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<title>bioRxiv Subject Collection: Developmental Biology</title>
<link>https://biorxiv.org</link>
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This feed contains articles for bioRxiv Subject Collection "Developmental Biology"
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<title>bioRxiv</title>
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<link>https://www.biorxiv.org</link>
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<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.05.756743v1?rss=1">
<title>
<![CDATA[
Fluid transport properties dominate blastocyst expansion over mechanics 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.05.756743v1?rss=1
</link>
<description><![CDATA[
Lumens populate most of our organs and their size, which dynamically changes throughout the day and lifetime, can influence their function. During mammalian development, the first lumen appears in the blastocyst. Surface epithelial cells pump ions to build an osmotic gradient that draws water, which inflates the embryo and stretches the epithelium as well as the zona pellucida, an elastic shell protecting the embryo. Blastocyst expansion is not steady and instead undergoes cycles of expansion interrupted by collapses during which the lumen leaks out. Early studies identified the critical role of osmotic pressure difference in regulating the expansion of the blastocyst whereas recent studies proposed that mechanical stresses would set the size of the embryo. However, the relative contributions of osmotic and mechanical stresses to lumen expansion dynamics remain unclear. Here, we investigate this using microfluidics, biophysics, machine learning and modelling on mouse embryos. Breaking down the expansion dynamics of mouse embryos, we discovered that fluid pumping rate accelerates, compensating for the increased frequency of collapses interrupting episodes of expansion. We reasoned that fluid transport could be rate limited by osmotic pumping, water permeability and/or mechanical constraints. Removing the mechanical constraint from the zona pellucida only marginally affected these expansion dynamics. Forcing fluid exchange with osmotic shocks we measured that water permeability is large enough not to restrict fluid accumulation rates. Finally, we estimate ion pumping for mouse blastocysts and interfere with it using inhibitors to measure how it quantitatively sets blastocyst expansion rates. Together, we propose that osmotic pressure differences, regulated by fluid transport properties, dominate over mechanical stresses in controlling blastocyst expansion dynamics.
]]></description>
<dc:creator><![CDATA[ Dagher, L., Bassanini, M., Deplater, L., Gropplero, G., Caporal, C., Maillot, A., Kastas, O., Duclut, C., Descroix, S., Maitre, J.-L. ]]></dc:creator>
<dc:date>2026-10-09</dc:date>
<dc:identifier>doi:10.64898/2026.10.05.756743</dc:identifier>
<dc:title><![CDATA[Fluid transport properties dominate blastocyst expansion over mechanics]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.08.757432v1?rss=1">
<title>
<![CDATA[
Mitochondrial amino acid export preserves mitochondrial volume at the egg-to-embryo transition 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.08.757432v1?rss=1
</link>
<description><![CDATA[
In animals, the transition from egg to embryo marks a rapid shift in cellular physiology, yet how mitochondria adapt to support this conversion remains poorly understood. We performed a targeted RNAi screen of conserved, nuclear-encoded mitochondrial proteins in Drosophila melanogaster to identify maternal effects. We identified distinct phenotypic classes affecting mitochondrial distribution or morphology in early embryos. We focused on Sideroflexin-1/3 (Sfxn1-3), a conserved mitochondrial inner membrane transporter, because it uniquely affects embryonic mitochondrial morphology. Maternal loss of Sfxn1-3 causes striking mitochondrial enlargement in embryos but not in oocytes, placing the trigger at the egg-to-embryo transition. Combining mitochondrial immunopurification with LC/MS-based metabolomic profiling, we show that amino acids are markedly enriched in Sfxn1-3-deficient mitochondria in both oocytes and embryos. This accumulation developmentally uncouples the metabolic and morphological phenotypes. By selectively disrupting discrete steps of egg activation, including translational activation, cell cycle re-entry, and fertilization, we demonstrate that mitochondrial swelling is independent of each, prompted instead by egg hydration. Beyond its reported role in proliferating cells as a serine importer, our data support a role for germline Sfxn1-3 in regulating inner mitochondrial membrane permeability to osmotically active amino acids. This activity is crucial for preserving organelle volume during the osmotic challenge of oocyte hydration. When this export fails, amino acid accumulation amplifies osmotic stress and drives rapid mitochondrial swelling. Together, these findings identify mitochondrial inner membrane permeability to amino acids as a key regulatory step that couples pre-established metabolite compartmentalization to osmotic adaptation at egg activation, and reveal how mitochondrial metabolic integrity and volume control are coordinated at this critical developmental transition.
]]></description>
<dc:creator><![CDATA[ Pamula, M. C., Clamon, L., Block, S., Savage, S., Gaebelein, C., Amarsanaa, A., Bisher, M., Mankus, D., Lytton-Jean, A., Kory, N., Lehmann, R. ]]></dc:creator>
<dc:date>2026-10-09</dc:date>
<dc:identifier>doi:10.64898/2026.10.08.757432</dc:identifier>
<dc:title><![CDATA[Mitochondrial amino acid export preserves mitochondrial volume at the egg-to-embryo transition]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.08.755167v1?rss=1">
<title>
<![CDATA[
TorPause: Efficient Static Organ Preservation for Transplants 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.08.755167v1?rss=1
</link>
<description><![CDATA[
Transplantation is limited by how long organs survive outside the body. Existing preservation methods slow metabolism or sustain physiological support, but neither eliminates ischemia-reperfusion injury (IRI), which shortens storage and drives organ discard. Embryonic diapause and hibernation show that mammalian cells retain a latent capacity for reversible metabolic arrest. Screening the PI3K-mTOR axis, we identified a dual inhibitor that pauses embryonic stem cells reversibly at ambient oxygen and holds intact mouse embryos in arrest for 11 days. Combined with a mitochondria-targeted hydrogen sulfide donor, this yields TorPause: a two-component flush pairing metabolic pausing with mitochondrial protection, compatible with existing preservation protocols. In a rat liver transplantation model, TorPause reduced structural injury and improved recipient survival after severe warm ischemic storage, potentially expanding the usable donor pool.
]]></description>
<dc:creator><![CDATA[ Bhadury, J., Tajima, T., Suchy, F. P., Masaki, H., Zhang, J., Rivera, M., Nishimura, T., Charlesworth, C. T., Esquivel, C. O., Nakauchi, H. ]]></dc:creator>
<dc:date>2026-10-09</dc:date>
<dc:identifier>doi:10.64898/2026.10.08.755167</dc:identifier>
<dc:title><![CDATA[TorPause: Efficient Static Organ Preservation for Transplants]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.06.756869v1?rss=1">
<title>
<![CDATA[
The dark transcriptome mouse organogenesis cell atlas 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.06.756869v1?rss=1
</link>
<description><![CDATA[
Single-cell atlases have transformed our understanding of mammalian tissue biology, yet the diverse noncoding "dark transcriptome" remains largely uncharted. Here, we present the Dark Transcriptome Mouse Organogenesis Cell Atlas (DT-MOCA), comprising 276,455 cells across embryonic days 11 to 18 and jointly capturing protein-coding transcripts and five major classes of noncoding RNAs through single-nucleus total RNA sequencing, establishing the first comprehensive catalog of noncoding RNAs across major cell types and developmental lineages. We found that long noncoding RNA and microRNA profiles distinguished major cell types and developmental lineages with resolution comparable to messenger RNA, whereas transfer RNA, small nuclear RNA, and small nucleolar RNA programs were less cell type-discriminative and more broadly shared. We further resolve noncoding RNA expression patterns as lineage-specific, temporally modulated, or coordinately regulated by cell identity and developmental stage. We observed that temporally regulated long noncoding RNAs were evolutionarily younger than those associated with cell identity. We further generate a catalog of the change of noncoding RNAs cross all 11 major developmental trajectories. It revealed lineage-specific coordination between transfer RNA supply and codon demand during musculoskeletal organogenesis as well as dynamic microRNA and small nucleolar RNA programs during the central nervous system development. We observed microRNAs converge on regulators of proliferation and gliogenesis and shared induction of Snord116 defining a developmental window relevant to Prader Willi syndrome. Together, this atlas provides a comprehensive catalog of the developmental dark transcriptome and reveals how noncoding RNA programs are organized across cell identity, developmental time, and lineage progression.
]]></description>
<dc:creator><![CDATA[ Liu, M., Zhang, D., Li, K., Kluger, Y., Lu, J., Gerstein, M. B., Li, H., Fan, R. ]]></dc:creator>
<dc:date>2026-10-09</dc:date>
<dc:identifier>doi:10.64898/2026.10.06.756869</dc:identifier>
<dc:title><![CDATA[The dark transcriptome mouse organogenesis cell atlas]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.05.756680v1?rss=1">
<title>
<![CDATA[
Ligand-specific endothelial Notch signaling coordinates brain pericyte specification and expansion 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.05.756680v1?rss=1
</link>
<description><![CDATA[
Pericyte specification and expansion must be coordinated with vascular growth to establish a functional cerebrovascular network, yet how endothelial signals control these distinct developmental transitions remains incompletely understood. Here, using genetic manipulation, single-cell transcriptomic analysis, and longitudinal in vivo imaging in zebrafish, we identify ligand-specific endothelial Notch signaling as a mechanism coordinating brain pericyte development. Endothelial Jag2b is required for efficient pericyte specification from pericerebral progenitor pools and subsequently promotes Notch-dependent pericyte proliferation and population expansion. By contrast, endothelial Dll4 restrains pericyte proliferation and functionally opposes Jag2b-dependent expansion, demonstrating that distinct endothelial Notch ligands generate different developmental outputs. Endothelial Notch activation increases jag2b expression, and genetic interaction analyses establish Jag2b as an important mediator of Notch-dependent pericyte expansion. Moreover, genetic disruption of piezo1 reduces brain pericyte abundance, whereas endothelial jag2b expression rescues this phenotype, placing Jag2b downstream of Piezo1-dependent hemodynamic signaling. Together, these findings reveal a ligand-specific endothelial Notch program that integrates hemodynamic cues with endothelial-pericyte communication to coordinate the specification and expansion of brain pericytes during cerebrovascular development.
]]></description>
<dc:creator><![CDATA[ Zhang, J., Zi, H., Dang, C., Sima, W., Li, X., Ning, G., Sun, L., Wang, Q. ]]></dc:creator>
<dc:date>2026-10-09</dc:date>
<dc:identifier>doi:10.64898/2026.10.05.756680</dc:identifier>
<dc:title><![CDATA[Ligand-specific endothelial Notch signaling coordinates brain pericyte specification and expansion]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.07.757370v1?rss=1">
<title>
<![CDATA[
Active maintenance of accessible chromatin at poised meiotic promoters by the NFYA-NURF axis is required for meiotic entry in mice 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.07.757370v1?rss=1
</link>
<description><![CDATA[
Developmental genes often acquire accessible chromatin prior to their activation, yet the mechanisms regulating this permissive state remain poorly understood. During spermatogenesis, many meiotic gene promoters display this poised state in spermatogonia, characterized by accessible promoters and paused RNA Pol II occupancy before their activation during meiosis. Here, we identify the NURF chromatin remodeling complex, comprised of SMARCA5 and its accessory subunit BPTF, as a key regulator of this process. We demonstrate that the transcription factor NFYA interacts with SMARCA5 and is required for its occupancy at poised meiotic gene promoters. Approximately one-third of poised meiotic gene promoters is co-occupied by NFYA, SMARCA5, and BPTF. Germline deletion of Smarca5 disrupts chromatin accessibility at poised meiotic promoters, impairs transcriptional program required for mitosis-to-meiosis transition, resulting in developmental arrest at meiotic entry. These findings identify NFYA-NURF as a key regulatory axis that regulates accessible chromatin at developmentally poised meiotic genes and primes them for activation later during meiosis.
]]></description>
<dc:creator><![CDATA[ Eghbali, A., Saflund, M., Askari, M., Abdi, M. M., Ostlund Farrants, A.-K., Yu, T., Ozata, D. M. ]]></dc:creator>
<dc:date>2026-10-09</dc:date>
<dc:identifier>doi:10.64898/2026.10.07.757370</dc:identifier>
<dc:title><![CDATA[Active maintenance of accessible chromatin at poised meiotic promoters by the NFYA-NURF axis is required for meiotic entry in mice]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.07.757402v1?rss=1">
<title>
<![CDATA[
A cellular atlas of Astyanax mexicanus embryogenesis reveals principles of developmental microevolution 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.07.757402v1?rss=1
</link>
<description><![CDATA[
The evolution of development is the primary mechanism by which morphological and functional diversity is generated. Comparing the developmental trajectories of single cells in entire embryos across species can reveal how gene expression is conserved and varies, as well as the molecular mechanisms underlying how cell- and tissue-specific changes in developmental regulation generate phenotypic differences. However, this perspective has not addressed the mechanisms of small-scale developmental microevolution, i.e, in closely-related species or even within a single species. The fish Astyanax mexicanus, which comes in two forms adapted to distinct environments - the eyed, river-dwelling morph and the eyeless, cave-adapted morph - is a remarkable model with which to investigate the evolution of gene regulation in a single species. Here, we generated and analyzed a single-nucleus RNA-seq atlas of the development of the two Astyanax morphs, from gastrula to swimming larva. Despite extensive changes in gene expression observed in the eight examined stages, for both ubiquitously-expressed and tissue-specific genes, and in both embryonic and extra-embryonic tissues, the temporal progression of cavefish and surface fish cells was similar in ordinal regression-based pseudotime models using 20-100 core genes. However, transcriptome-wide comparisons of gene expression waves revealed massive heterochronic shifts. In cavefish, some tissues had a majority of genes lagging behind in their transcriptional dynamics (e.g. the optic region), while in others, a majority of genes had accelerated dynamics (e.g. the mesoderm), or else, an equivalent number of genes were found in either category (e.g. the endoderm). Furthermore, cell fate acquisition and differentiation were variably affected in different cavefish lineages, with delays of ~6 hours in the retina, ~2 hours in the axial mesoderm and ~none in the extra-embryonic enveloping layer. Thus, cavefish embryos progress as a mosaic of different tissues, or modules, each following its own transcriptional tempo. Because gene expression differential regulation and time shifts were more prevalent in the early stages and gradually diminished throughout development, we propose that cavefish embryos initially undergo strong decanalisation before becoming re-canalized in line with the shared Astyanax developmental program.
]]></description>
<dc:creator><![CDATA[ Roig Puiggros, S., Royer, G., Prados, J., AGNES, F., Leclercq, J., Jabaudon, D., Torres-Paz, J., RETAUX, S. ]]></dc:creator>
<dc:date>2026-10-09</dc:date>
<dc:identifier>doi:10.64898/2026.10.07.757402</dc:identifier>
<dc:title><![CDATA[A cellular atlas of Astyanax mexicanus embryogenesis reveals principles of developmental microevolution]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.07.757239v1?rss=1">
<title>
<![CDATA[
A tissue-targeted auxin-inducible degradation toolkit for C. elegans embryogenesis 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.07.757239v1?rss=1
</link>
<description><![CDATA[
Many proteins required for embryogenesis are expressed in multiple tissues and across developmental time, often with tissue- and stage-specific roles. To resolve where and when proteins function, we developed a tissue-targeted auxin-inducible degradation toolkit for C. elegans embryogenesis. We generated a plasmid set compatible with single-copy insertion or high-copy extrachromosomal array generation that employs tissue-specific promoters (active in the germline, intestine, muscle, pharynx, neuroblasts, neurons, sensory neurons, epidermis, and pan soma) to drive an operon expressing an optimized auxin-dependent plant F-box factor TIR1 and, in most cases, a fluorescent histone. Using a ubiquitous nuclear envelope marker as a test substrate, we identified single-copy insertions and arrays that exhibit efficient auxin-dependent, tissue-specific target degradation. We also establish a workflow that ensures all functionally important isoforms of a target are tagged and that degradation reproduces the loss-of-function phenotype prior to tissue-specific analysis. Applying the toolkit to the broadly expressed Rho kinase LET-502, we find that degradation in the epidermis, but not in other embryonic tissues, disrupts elongation. Unexpectedly, temporal analysis revealed that LET-502 is required for late as well as early elongation.
]]></description>
<dc:creator><![CDATA[ Varshney, N., Green, R. A., Desai, A. O., Moghareh, S., Green, D. J., Desai, A., Oegema, K. ]]></dc:creator>
<dc:date>2026-10-09</dc:date>
<dc:identifier>doi:10.64898/2026.10.07.757239</dc:identifier>
<dc:title><![CDATA[A tissue-targeted auxin-inducible degradation toolkit for C. elegans embryogenesis]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.07.757307v1?rss=1">
<title>
<![CDATA[
A Novel Role for FSTL-1 in Hematopoietic Stem Cell Homeostasis and Post-injury Regeneration 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.07.757307v1?rss=1
</link>
<description><![CDATA[
Background: The ability to repopulate all lineages of blood cells from a single hematopoietic stem cell (HSC) requires a constant balancing between maintenance of quiescence/self-renewal and the need for differentiation and adoption of specific lineage phenotypes. A classical interpretation suggests that during homeostasis, long- and then short-term HSCs differentiate into multipotent progenitors (MPPs), which then lack self-renewal capacity but can still differentiate into all downstream lineages. While much is known about the intrinsic and extrinsic regulators that promote HSC homeostasis, less is known about factors which influence HSC behavior following significant bone marrow (BM) injury, such as sublethal irradiation (SLI). Methods: Conditional knock-out of follistatin-like 1 (FSTL-1) was achieved by breeding mice with floxed Fstl1 sites to mice expressing CreERT2 under control of the ROSA locus, followed by systemic tamoxifen administration. ELISA and RT-PCR quantitated protein and RNA level loss of FSTL-1, respectively. HSC populations were assessed by flow cytometry under multiple conditions. Sublethal irradiation induced BM injury and blocking polyclonal FSTL-1 antibodies were used to recapitulate results seen with genetic ablation. Finally, single cell RNA sequencing defined both cell-specific expression of Fstl1 within the BM compartment, but also identified transcripts and pathways upregulated in the absence of FSTL-1. Results: These studies delineate a novel role for FSTL-1 in regulating HSC biology. In addition to selective expression of Fstl1 within HSCs, genetic deletion of Fstl1 increases Lineage negative;Sca-1+c-Kit+ (LSK) cell number and alters HSC homeostasis. These findings are further amplified in the BM in the context of recovery from sublethal irradiation. Importantly, the post-irradiation increase in BM cellularity seen with Fstl1 deletion is replicated by treatment with anti-FSTL-1 polyclonal antibodies. Finally, single cell RNA sequencing reveals distinct Fstl1 expression in specific LSK subpopulations, including HSCs and proliferating cells, and identifies a novel relationship between decreased FSTL-1 levels and enrichment of canonical metabolic pathways including oxidative phosphorylation, fatty acid metabolism, and glycolysis. Conclusions: Taken together, these results highlight a novel role for FSTL-1 in promoting HSC homeostasis. They also unlock an innovative way to promote HSPC recovery following BM injury, knowledge predicted to be of significant therapeutic value.
]]></description>
<dc:creator><![CDATA[ Byersdorfer, C., Henkel, M., Sugitani, N., Lou, D., Chen, K., Campfield, B. T. ]]></dc:creator>
<dc:date>2026-10-09</dc:date>
<dc:identifier>doi:10.64898/2026.10.07.757307</dc:identifier>
<dc:title><![CDATA[A Novel Role for FSTL-1 in Hematopoietic Stem Cell Homeostasis and Post-injury Regeneration]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-09</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.01.755929v1?rss=1">
<title>
<![CDATA[
Facing West Africa's rosewood crisis: what determines the success of preserving and propagating the endangered barwood (Pterocarpus erinaceus)? A multi-model test of site and maternal-origin effects 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.01.755929v1?rss=1
</link>
<description><![CDATA[
Pterocarpus erinaceus Poir. (Fabaceae), the barwood or vene, is at the heart of one of the most severe conservation crises currently affecting tropical timber species. It has become the most heavily traded timber species in the world by volume, at the centre of an illegal rosewood trade to Asia that has driven the species to near-total disappearance in several countries despite its listing on CITES Appendix II since 2016. Faced with this urgency, ex situ conservation and restoration programmes often rest on the untested assumption that selecting seed trees by size improves the quality of the offspring produced in the nursery. This study rigorously tests this hypothesis against the competing one of a determinism dominated by the planting site, using six complementary analytical approaches (continuous regression, linear mixed models with a site x seed-tree interaction, seed-mass mediation analysis, non-linear growth modelling of height and diameter, between-site phenotypic plasticity, and multi-predictor allometric equations), across two contrasting bioclimatic sites in COte d'Ivoire (Korhogo: dry zone; Daloa: humid zone) and six seed-tree categories. Site exerts a decisive influence on growth at all ages (ANOVA, p<0.001 for height, diameter and biomass), whereas germination does not differ significantly between sites (70.3% at Daloa versus 61.6% at Korhogo; X2=1.95; p=0.162). Seed-tree DBH does not affect growth in any of the tests (continuous regression, p>0.30; mixed model, p>0.07), and the seed-mass mediation analysis remains inconclusive, seed mass varying only slightly among seed trees in this species (0.07-0.08 g). The exponential growth model provides the best fit for height and diameter at both sites, and two-predictor allometric equations explain 96.2% of biomass variance compared with 89.9% for the single-predictor model. These results indicate that ex situ conservation and compensatory reforestation programmes for this endangered species would benefit from prioritising the choice of planting site over the dendrometric selection of seed trees. A recommendation directly applicable to conservation nurseries established in response to the rosewood crisis.
]]></description>
<dc:creator><![CDATA[ Adji, B. I. ]]></dc:creator>
<dc:date>2026-10-07</dc:date>
<dc:identifier>doi:10.64898/2026.10.01.755929</dc:identifier>
<dc:title><![CDATA[Facing West Africa's rosewood crisis: what determines the success of preserving and propagating the endangered barwood (Pterocarpus erinaceus)? A multi-model test of site and maternal-origin effects]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.06.757014v1?rss=1">
<title>
<![CDATA[
Temperature scaling of developmental tempo reveals reaction-dominated morphogen patterning 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.06.757014v1?rss=1
</link>
<description><![CDATA[
A central question in developmental biology is how embryonic patterning remains robust when developmental tempo changes. In ectotherms, temperature strongly alters developmental speed and biochemical reaction rates, whereas diffusion is expected to change only weakly. How morphogen gradients required for patterning remain correctly scaled under these conditions is unclear. We addressed this problem in medaka embryos by quantifying developmental speed, morphogen clearance, diffusion, and endogenous Nodal dynamics across a broad temperature range. Developmental tempo, morphogen production, clearance, and tissue movement increased approximately two- to threefold per 10{degrees}C, whereas effective morphogen diffusion remained largely unchanged. Despite this mismatch, germ-layer proportions and morphogen patterning remained robust. Our mathematical simulations suggest that this robustness arises because the system operates in a reaction-dominated regime, in which changes in reaction and growth kinetics - rather than diffusion - are sufficient to rescale morphogen gradients. Together, our experiments and simulations provide new insights into how morphogen gradients adjust to maintain accurate tissue patterning across changes in developmental time and tempo.
]]></description>
<dc:creator><![CDATA[ Capek, D., Eich, T., Kögler, A., Morales-Navarrete, H., Riabtsev, O., Thumberger, T., Floeth, L., Bihler, J., Bajoghli, B., Wittbrodt, J., Müller, P. ]]></dc:creator>
<dc:date>2026-10-07</dc:date>
<dc:identifier>doi:10.64898/2026.10.06.757014</dc:identifier>
<dc:title><![CDATA[Temperature scaling of developmental tempo reveals reaction-dominated morphogen patterning]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.06.757095v1?rss=1">
<title>
<![CDATA[
PHC2-Dependent PRC1 Assemblies Stabilize Motor Neuron Hox Codes 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.06.757095v1?rss=1
</link>
<description><![CDATA[
Polycomb Repressive Complexes PRC1 and PRC2 establish and maintain chromatin architectures critical for cell-type specific gene expression. In the developing spinal cord, PRC1 is essential for implementing Hox-dependent transcriptional programs that diversify motor neuron identities. Although PRC1 can assemble into subnuclear condensates, whether these structures contribute to the specification and maintenance of neuronal subtype fates remains unclear. Using chick and mouse models, we show that canonical PRC1 components - BMI1, PHC2, CBX2, RING1B - coalesce into subnuclear assemblies as neural progenitors differentiate into motor neurons. Disrupting PHC2 polymerization in either neural progenitors or postmitotic neurons dismantles BMI1-containing PRC1 assemblies, triggering derepression of caudal Hox genes and a cell autonomous loss of segment-specific motor neuron fates. Mouse mutants lacking the core PRC1 subunit Ring1 fail to form BMI1-containing assemblies, despite intact PHC2 and CBX2 polymers. In contrast, motor neuron-restricted deletion of core PRC2 subunits (Ezh1/2) depletes H3K27me3 histone marks but retains PRC1 assemblies and Hox boundaries. Together, these findings indicate that PHC2-dependent PRC1 assemblies stabilize Hox transcriptional boundaries and motor neuron segmental identities.
]]></description>
<dc:creator><![CDATA[ Miller, A. K., Sawai, A., Cavanagh, A. E., Dasen, J. S. ]]></dc:creator>
<dc:date>2026-10-07</dc:date>
<dc:identifier>doi:10.64898/2026.10.06.757095</dc:identifier>
<dc:title><![CDATA[PHC2-Dependent PRC1 Assemblies Stabilize Motor Neuron Hox Codes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.06.756974v1?rss=1">
<title>
<![CDATA[
Lineage tracing reveals asynchronous fate restriction in mouse embryos and stem cell-derived embryo models 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.06.756974v1?rss=1
</link>
<description><![CDATA[
How a flexible mammalian embryo gives rise to a reproducible body plan remains unclear, partly because cell lineages cannot be followed continuously in vivo. We combined DNA Typewriter lineage recording with tetraploid complementation to reconstruct high-resolution single-cell genealogies across mouse development and built FateVec, an analysis framework that infers fate-bias dynamics and lineage-associated transcriptional programs from reconstructed phylogenies. Loss of developmental potential proved progressive and asynchronous, with multiple lineages acquiring detectable fate bias before morphological diversification at gastrulation. Within the neural crest, most cells remained multipotent over an extended window, while independent founder clades differed markedly in restriction timing. Extending lineage recording to a stem-cell-derived embryo model revealed that cells with shared transcriptional identities can arise from distinct lineage relationships. We further found embryonic-lineage contributions to extraembryonic-like states, exposing an unexplored lineage plasticity. This lineage-resolved view of embryogenesis reveals that cell identity alone predicts neither developmental ancestry nor the timing of fate restriction.
]]></description>
<dc:creator><![CDATA[ Liu, Y., Park, J., Amaya, L., Junyent, S., Sun, X., Xiao, J. S., Wang, Y., Wang, H., Lu, Y., Nakagawa, S., Park, S.-E., Hu, W., Liu, S., Wei, J., Kim, H. H., Thomson, M., Ju, C.-W., Bronner, M. E., Choi, J., Zernicka-Goetz, M. ]]></dc:creator>
<dc:date>2026-10-07</dc:date>
<dc:identifier>doi:10.64898/2026.10.06.756974</dc:identifier>
<dc:title><![CDATA[Lineage tracing reveals asynchronous fate restriction in mouse embryos and stem cell-derived embryo models]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-07</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.06.756938v1?rss=1">
<title>
<![CDATA[
Sample preparation optimisation for array tomography volume EM of entire organisms: a case study for marine larvae 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.06.756938v1?rss=1
</link>
<description><![CDATA[
Serial-sectioning electron microscopy allows the exploration of the 3D ultrastructure of cells, tissues or whole organisms. Sample preparation is a critical step for this technique, which determines the quality of downstream imaging and analysis. Here we optimize a high-pressure freezing sample-preparation workflow for larvae of the marine annelid Platynereis dumerilii. We tested several fixation and staining methods and screened a large number of specimens by synchrotron X-ray imaging to evaluate specimen integrity and contrast. We further evaluated selected blocks by array tomography SEM to select the best performing protocols. Our protocols and robust workflow could be adapted to similar marine planktonic organisms including ciliated invertebrate larvae.
]]></description>
<dc:creator><![CDATA[ Szabo, K., Kerbl, A., Mocaer, K., Svetlove, A., Pacureanu, A., Jekely, G. ]]></dc:creator>
<dc:date>2026-10-06</dc:date>
<dc:identifier>doi:10.64898/2026.10.06.756938</dc:identifier>
<dc:title><![CDATA[Sample preparation optimisation for array tomography volume EM of entire organisms: a case study for marine larvae]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-06</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.03.756328v1?rss=1">
<title>
<![CDATA[
DDR and TMEM132 genes control progenitor targeting and regenerative assembly of the planarian eye 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.03.756328v1?rss=1
</link>
<description><![CDATA[
How progenitors can faithfully self-assemble to build new organs in adulthood is a central unsolved problem in regeneration biology. The planarian eye is a model for uncovering principles of de novo organogenesis during regeneration. In this process, pluripotent adult stem cells specify into ovo+ migratory progenitors which target to the eye field due to Wnt and FGFRL signals produced from bodywall muscle, then differentiate into photoreceptor neurons (PRNs) and pigmented optic cup (OC) cells, followed by organization of these two cell types in an opposing pattern that completes eye organ maturation. We used scRNA-seq to characterize eye progenitor transcriptomes during regeneration, followed by FISH validation, and RNAi screening to identify regulators of eye regeneration. This uncovered a function for the discoidin domain receptor ddr-1 in preventing the premature terminal differentiation of migratory eye progenitors. DDRs encode collagen receptors, and bodywall muscle is the major source of collagen in planarians, suggesting eye progenitors likely interface with muscle ECM for their proper deployment in regeneration. We further identified a novel eye morphogenesis phenotype from knockdown of tmem132-1, causing failed heterotypic adhesion between eye cell types. TMEM132 factors are conserved cell-surface receptors that mediate adhesion and regulate migration, and human TMEM132 mutations are associated with several neurobehavioral diseases. Therefore, planarian tmem132-1 likely directly regulates the capture and assembly of migratory progenitors into mature eyes during regeneration. Together, these results define new steps in the eye regeneration pathway and suggest ancient roles for DDR and TMEM132 in progenitor migration and coordinated organ assembly.
]]></description>
<dc:creator><![CDATA[ Place, C., Lo, K. C., Clark, E. G., Petersen, C. P. ]]></dc:creator>
<dc:date>2026-10-06</dc:date>
<dc:identifier>doi:10.64898/2026.10.03.756328</dc:identifier>
<dc:title><![CDATA[DDR and TMEM132 genes control progenitor targeting and regenerative assembly of the planarian eye]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-06</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.05.756835v1?rss=1">
<title>
<![CDATA[
Spatially restricted bmp16 in an extra-embryonic syncytium promotes dorsoventral patterning 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.05.756835v1?rss=1
</link>
<description><![CDATA[
How nuclei within a shared cytoplasm organize gene expression programs to direct developmental signaling remains incompletely understood. Here, we combine single-nucleus RNA sequencing, spatial transcriptomic mapping, and functional perturbations to characterize the zebrafish yolk syncytial layer (YSL), an extra-embryonic syncytium that supports embryonic development and patterning. We identify extensive transcriptional covariation among YSL nuclei, revealing coordinated multigene programs organized along dorsoventral and animal-vegetal axes. Within the YSL, we identify an animal-ventral subdomain expressing several BMP ligand transcripts including bmp16, a member of the BMP2/4 subfamily. We found bmp16 expression to be exclusively extra-embryonic during gastrulation, and functional perturbations reveal that bmp16 is sufficient to ventralize embryos upon overexpression and acts synergistically with bmp2b to promote ventral fates. Ventral YSL expression of Bmp transcripts depends on a transcriptional program downstream of mxtx2 and is maintained independently of BMP pathway autoregulation, while negative regulation by hhex restricts bmp16 expression to the ventral YSL. Together, these findings establish the YSL as a spatially organized syncytium in which coordinated nuclear gene expression programs support localized sources of embryonic patterning signals.
]]></description>
<dc:creator><![CDATA[ Couturier, H., Greenfeld, H., Zussman, J. W., Wagner, D. E. ]]></dc:creator>
<dc:date>2026-10-06</dc:date>
<dc:identifier>doi:10.64898/2026.10.05.756835</dc:identifier>
<dc:title><![CDATA[Spatially restricted bmp16 in an extra-embryonic syncytium promotes dorsoventral patterning]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-06</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.05.756028v1?rss=1">
<title>
<![CDATA[
In situ identification of pre-hematopoietic stem cells and their niche 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.05.756028v1?rss=1
</link>
<description><![CDATA[
Definitive hematopoietic stem cells (HSCs) emerge predominantly along the ventral surface of the dorsal aorta in the embryonic aorta-gonad-mesonephros (AGM) region, yet the spatial organization of the niche underlying this developmental asymmetry remains poorly understood. Defining the native niche of pre-HSCs has also been hindered by their rarity, transient nature and lack of a single definitive marker for their identification in situ. Here, we integrated single-cell and spatial transcriptomics to construct a spatiotemporal atlas of the niche in the AGM. Neural cells and chondrogenic mesenchyme predominated dorsally, whereas N-cadherin mesenchymal stromal cells (N-cad+ MSCs) formed a ventral layer between the aortic endothelium and mesonephric cells. BMP and SHH signaling showed overall dorsal enrichment, whereas WNT, NOTCH and KIT signaling were enriched ventrally, with these cellular and signaling patterns dynamically remodeled across HSC ontogeny. Imaging-based spatial transcriptomics validated the findings and further enabled the identification of individual pre-HSCs in situ and revealed a multicellular niche comprising endothelial cells, N-cad+ MSCs, intra-aortic hematopoietic cluster cells and macrophages. TGF{beta} and NOTCH signals were primarily supplied locally, whereas major sources of BMP and WNT were more distant. Functional perturbation identified niche-derived CD200 as an immune-regulatory signal promoting HSC development, validating a spatially predicted niche interaction. Together, our findings link tissue-scale spatial organization with the local multicellular niche supporting the preferential development of HSCs along the ventral aorta.
]]></description>
<dc:creator><![CDATA[ Mao, X., Zhang, N., Bennett, L., He, X., Scott, A., Hall, K., Petentler, K., Malloy, S., Huang, S., Kroesen, A., McKinney, S., Ploumakis, A., Yang, Z., Dong, R., Javier, J., Haug, J., Li, H., Yu, Z., Perera, A., Vlachos, I., Chen, F., Trainor, P., Speck, N. A., Li, L. ]]></dc:creator>
<dc:date>2026-10-06</dc:date>
<dc:identifier>doi:10.64898/2026.10.05.756028</dc:identifier>
<dc:title><![CDATA[In situ identification of pre-hematopoietic stem cells and their niche]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-06</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.05.755686v1?rss=1">
<title>
<![CDATA[
Integrin α3β1 is required for alveolar-capillary barrier formation through regulation of epithelial differentiation 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.05.755686v1?rss=1
</link>
<description><![CDATA[
Laminin-binding integrins regulate critical morphogenic processes, but their specific roles in lung development are unknown. In this study, we combined an in vivo model of epithelial 3 subunit deletion in the murine lung with a multiomics approach to investigate the role of the epithelial 3{beta}1 integrin during murine lung development. We demonstrate that 3{beta}1 integrin is dispensable for airway branching morphogenesis due to delayed epithelial expression. Instead, in vivo deletion of 3{beta}1 integrin impaired alveolar epithelial cell differentiation and disrupted alveolar-capillary barrier formation, functionally limiting gas exchange. A discontinuous alveolar BM contained abnormal collagen IV and laminin networks and widened the gap between epithelial and endothelial cells in the alveolar-capillary barrier niche. Mechanistically, mice deficient in epithelial 3{beta}1 integrin possessed an intracellular trafficking and secretion defect for BM components. Thus, integrin 3{beta}1 orchestrates the temporal maturation of alveolar epithelial cells required for organization of the alveolar-capillary barrier.
]]></description>
<dc:creator><![CDATA[ Henry, A. D., Alwine, A. L., Niederhuber, M. J., Yarlagadda, A. K., Muthakana, N. R., Mordant, A. L., Gokey, J. J., Sucre, J. M. S., Hepperla, A. J., Cartailler, J.-P., Gulleman, P. M., Sharkey, A. L., Boatwright, N., Kook, S., Lee, J. C., Jetter, C. S., Shirazi, S. P., Newcomb, D. C., Hart, R. C., Reese, J. J., Sonnenberg, A., Lennon, R., Blackwell, T. S., Zent, R., Plosa, E. ]]></dc:creator>
<dc:date>2026-10-06</dc:date>
<dc:identifier>doi:10.64898/2026.10.05.755686</dc:identifier>
<dc:title><![CDATA[Integrin α3β1 is required for alveolar-capillary barrier formation through regulation of epithelial differentiation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-06</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.04.756557v1?rss=1">
<title>
<![CDATA[
Adenosine refines the balance of spermatogonial proliferation and differentiation 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.04.756557v1?rss=1
</link>
<description><![CDATA[
The balance between spermatogonial proliferation and differentiation is essential for sustaining male fertility, yet the contribution of cellular metabolism remains poorly understood. Here, we showed that adenosine levels increased significantly during spermatogonial differentiation and promoted the formation of differentiating spermatogonia. Using a conditional knockout mouse model in which Ahcy, a gene encoding an enzyme in adenosine synthesis, is deleted from spermatogonia, we found that disruption of adenosine generation blocked spermatogonial differentiation, resulting in a transient delay in spermatogenesis. We further demonstrated that adenosine exerted its effects partially through ADORA2A- and ADORA2B-mediated signaling. Downregulating these receptor activities by specific inhibitors in spermatogonial culture or by genetic ablation in mice led to increased spermatogonial proliferation. Taken together, our study identified adenosine as a metabolic signal in refining the balance between spermatogonial proliferation and differentiation, linking cellular metabolism to critical developmental timing and stem cell fate decisions.
]]></description>
<dc:creator><![CDATA[ Wang, P., Nguyen, D., Xiao, C., Xu, Y., Hu, B., Zhang, Z., Reitman, M., WANG, Y. ]]></dc:creator>
<dc:date>2026-10-06</dc:date>
<dc:identifier>doi:10.64898/2026.10.04.756557</dc:identifier>
<dc:title><![CDATA[Adenosine refines the balance of spermatogonial proliferation and differentiation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-06</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.05.756652v1?rss=1">
<title>
<![CDATA[
Disentangling maternal pregnancy and fetal-specific plasma signatures through integrated proteomics and site-specific N-glycoproteomics 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.05.756652v1?rss=1
</link>
<description><![CDATA[
During pregnancy, mother and fetus co-exist albeit as two physiologically distinct individuals, connected through the placenta and the umbilical cord. This connection allows for the exchange of vital substances, while individual blood homeostasis remains intact. We hypothesized that comparing maternal and cord plasma (N-glyco)proteomes would provide insights into the biological communication and unique physiological state of each individual. As comparing only matched maternal and umbilical cord blood plasma misses a crucial identifier in determining whether observed changes are related to infancy, pregnancy or both, we designed a triad study by adding a non-pregnant women control group. This allowed us to distinguish pregnancy-specific proteins and their potentially altered N-glycosylation from those in infancy. We found that the fetus and mother have distinct proteomes, N-glycoproteoforms and alternative complement regulation. Moreover, we observed that pregnancy in women led to specific N-glycosylation changes on a select set of primarily HDL-associated and acute-phase proteins. Lastly, our data provide evidence for an early fetal development of the humoral immune system as especially fetal IgM displayed distinctive N-glycosylation signatures.
]]></description>
<dc:creator><![CDATA[ Jager, S., Kalaidopoulou Nteak, S., Reznikov, G., Rodrigues Ianiski, F., Visser, R., Sinitcyn, P., Vidarsson, G., Heck, A. J. R. ]]></dc:creator>
<dc:date>2026-10-06</dc:date>
<dc:identifier>doi:10.64898/2026.10.05.756652</dc:identifier>
<dc:title><![CDATA[Disentangling maternal pregnancy and fetal-specific plasma signatures through integrated proteomics and site-specific N-glycoproteomics]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-06</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.01.755350v1?rss=1">
<title>
<![CDATA[
Epigenetic regulators partition the genome by evolutionary and developmental constraint 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.01.755350v1?rss=1
</link>
<description><![CDATA[
Many epigenetic regulators play essential roles in animal development, but precisely how they function across different cell types without clear sequence preferences remains a foundational challenge. Here, we employed single-cell RNA sequencing to survey the mutant phenotypes of 30 essential regulatory pathways across over 450 gastrulation stage mouse embryo replicates, including essential factors associated with repressive chromatin states, RNA surveillance/processing, and other genomic roles. We then use this integrated manifold to partition mutant responses into a developmentally-resolved interaction network, revealing a hierarchy of heterochromatin-associated interactions that act orthogonally to Polycomb Repressive Complex-mediated control of embryo patterning. Compared to the embryo proper, we find that the developing placenta and yolk sac can accommodate broad swings in repetitive element expression, a resilience in keeping with the relative evolutionary recency and phenotypic plasticity of these tissues. Dense temporal sampling of Human Silencing Hub (HUSH) mutant embryogenesis further supports the notion that the gastrulating embryo is particularly constrained and depends on multiple layers of insulation, including the need to suppress evolutionarily young genetic elements to stably license highly conserved, phylotypic programs. In combination, our work highlights the power of single cell-resolved developmental genetics to contextualize the roles of epigenetic regulators, which restrict genomic action to support robust cellular identities and embryological forms.
]]></description>
<dc:creator><![CDATA[ Kijima, Y., Villagrana, J., Wang, M., Tornisiello, R., Dias, N., Hou, J. T.-C., Tse, K., Wang, J., Kretzmer, H., Sumigray, K., Aktas, T., Smith, Z. ]]></dc:creator>
<dc:date>2026-10-02</dc:date>
<dc:identifier>doi:10.64898/2026.10.01.755350</dc:identifier>
<dc:title><![CDATA[Epigenetic regulators partition the genome by evolutionary and developmental constraint]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.01.755984v1?rss=1">
<title>
<![CDATA[
Optogenetic BMP4 models symmetry breaking and primitive streak formation in hPSCs 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.01.755984v1?rss=1
</link>
<description><![CDATA[
Gastrulation begins when the epiblast epithelium breaks symmetry to form the primitive streak, but current in vitro models neither fully capture this process nor separate its mechanical and chemical inputs. Here, we introduce LightBMP, an optogenetic platform that enables spatiotemporally programmable BMP4 expression in human pluripotent stem cells. Dose and duration control reveal a sustained low-BMP regime, inaccessible to recombinant ligand, that specifies mesoderm. Spatially programmed BMP4 sources in uniform cultures mimic the radial organization of 2D gastruloids, showing that mechan-ical context and edge sensing are not required for patterning. In micropatterned colo-nies, light-defined sources break symmetry to generate a stripe-shaped, primitive-streak-like domain where cells acquire multiple mesodermal fates and undergo directed migration. Together, these results show that spatial control of a single morphogen source is sufficient to drive symmetry breaking and primitive-streak-like patterning, independent of edge constraints.
]]></description>
<dc:creator><![CDATA[ Streletskaia, A., Bashor, C. J., Warmflash, A. ]]></dc:creator>
<dc:date>2026-10-02</dc:date>
<dc:identifier>doi:10.64898/2026.10.01.755984</dc:identifier>
<dc:title><![CDATA[Optogenetic BMP4 models symmetry breaking and primitive streak formation in hPSCs]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.02.755877v1?rss=1">
<title>
<![CDATA[
microRNAs control temporal patterning of the vertebrate nervous system 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.02.755877v1?rss=1
</link>
<description><![CDATA[
Temporal patterning is essential for generation of neuronal diversity in the developing vertebrate nervous system. A shared sequence of temporal transcription factors (tTFs) partitions neurons by birth date across much of the central nervous system. The molecular mechanisms that control the timing of expression of these tTFs are incompletely understood. Here, we provide evidence that this process is under the control of microRNAs (miRNAs). Perturbing miRNA biogenesis by conditional deletion of Dgcr8 from the developing mouse nervous system extends the window during which neurons with early identities are generated, but abolishes late identities in the spinal cord, hindbrain and midbrain, and holds progenitors in an early transcriptional state. We further identify miRNAs of the let-7 and miR-9 families, which target transcriptional regulators of early progenitor and neuronal identities, as candidates for mediating this effect. Throughout the nervous system, levels of these miRNAs rise during the neurogenic period in progenitors, while levels in neurons correlate with their birth-date. Moreover, the sensitivity of tTF-encoding transcripts to miR-9 inversely correlates with their expression sequence, suggesting a model in which miR-9 controls the chronology of neuronal cell fate transitions by targeting specifiers of early progenitor and neuronal temporal identity in a level-dependent manner. Consistently, perturbations of miR-9 expression dynamics by gain and loss-of-function approaches perturb temporal patterning. Together, our results demonstrate a critical, evolutionary conserved role for miRNAs in temporal patterning and suggest that a temporal miR-9 expression gradient controls the timing of tTF expression in large parts of the developing vertebrate nervous system.
]]></description>
<dc:creator><![CDATA[ Renaux, E., Caudet Segarra, L., Mistry, A. S., Pandey, M., Sagner, J., Jäck, H.-M., Wittmann, J., Wegner, M., Sagner, A. ]]></dc:creator>
<dc:date>2026-10-02</dc:date>
<dc:identifier>doi:10.64898/2026.10.02.755877</dc:identifier>
<dc:title><![CDATA[microRNAs control temporal patterning of the vertebrate nervous system]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.10.03.756416v1?rss=1">
<title>
<![CDATA[
Notch1 and Notch2 receptors mediate the prosensory functions of the Notch ligand Jagged1 in the mammalian cochlea 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.10.03.756416v1?rss=1
</link>
<description><![CDATA[
Mechanosensory hair cells in the cochlea of the inner ear are essential for sound detection. Previous studies have shown that loss of the Notch ligand Jagged1 (JAG1) disrupts maintenance of prosensory progenitors, from which hair cells and their surrounding supporting cells derive. However, the molecular and cellular mechanisms by which JAG1 regulates prosensory progenitor maintenance are poorly understood, and the Notch receptors that mediate this function in the developing cochlea remain unknown. To address this, we generated Jag1 conditional knockout mice and characterized their prosensory deficits using transcriptomic and phenotypic analyses. We show that JAG1 loss abolishes prosensory expression of CDKN1B (p27Kip1) and reduces expression of essential neurotrophic factors, thereby disrupting the stereotyped pattern of cell-cycle exit and innervation within the prosensory domain. Furthermore, conditional knockout of Notch1 and Notch2 (Notch1/2) receptors in supporting cells phenocopied the Jag1 deletion phenotype, showing both a severe reduction in outer hair cell formation and a disrupted pattern of cell-cycle exit and innervation, thereby confirming their essential roles in mediating the prosensory functions of JAG1.
]]></description>
<dc:creator><![CDATA[ Huang, H., Li, X., Venhaus, E., Doetzlhofer, A. ]]></dc:creator>
<dc:date>2026-10-05</dc:date>
<dc:identifier>doi:10.64898/2026.10.03.756416</dc:identifier>
<dc:title><![CDATA[Notch1 and Notch2 receptors mediate the prosensory functions of the Notch ligand Jagged1 in the mammalian cochlea]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-05</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.09.28.754901v1?rss=1">
<title>
<![CDATA[
Shade enhancers, a class of redundant enhancers uncovered by functional JAK-STAT pathway dissection 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.09.28.754901v1?rss=1
</link>
<description><![CDATA[
JAK-STAT signalling pathway activation relies mostly on the transcriptional regulation of its ligands. The pathway, conserved in vertebrates and invertebrates, is required for the development and homeostasis of various organs. In contrast to the complexity of the vertebrate pathway, with a multiplicity of ligands, receptors, kinases and transcription factors, the simplicity of the Drosophila pathway with only three ligands (Upd1, Upd2 and Upd3), a single receptor (Dome), a JAK kinase (Hop) and a STAT transcription factor (STAT92E) facilitates the genetic study of its multiple functions. To discover how, when and where the Upd1 ligand performs each organogenetic function, we have searched for the different enhancers controlling its dynamic spatio-temporal regulation and used them to generate minigenes replicating specific stages of Upd1 expression. The combination of these minigenes with mutations deleting all three Upd ligands, allowed us to identify the timing when the various embryonic functions are mediated, including head involution, tracheae, corpora allata and prothoracic gland specification, posterior spiracle formation and hindgut elongation. We uncover most of the enhancers controlling STAT activation during embryonic organogenesis and those driving activation in the adult testis and the ovary. As expected, we identified redundant shadow enhancers but, interestingly, we found a different type of redundant enhancers that mediate identical developmental functions although driving completely different expression patterns. We name this new class of functionally redundant enhancers driving different expression as shade enhancers. We propose shade enhancers provide evolutionary plasticity as they could allow the pattern of gene expression to diversify without altering the underlying body plan.
]]></description>
<dc:creator><![CDATA[ Sanchez-Higueras, C., Terron-Gonzalez, L., Barcenilla-Merino, D., Garcia-Ferres, M. S., Marrufo-Mena, A., Sotillos, S., C-G Hombria, J. ]]></dc:creator>
<dc:date>2026-10-02</dc:date>
<dc:identifier>doi:10.64898/2026.09.28.754901</dc:identifier>
<dc:title><![CDATA[Shade enhancers, a class of redundant enhancers uncovered by functional JAK-STAT pathway dissection]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.09.30.755600v1?rss=1">
<title>
<![CDATA[
Increased stress in early life epigenetically rewires pathways related to aging and longevity 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.09.30.755600v1?rss=1
</link>
<description><![CDATA[
Environmental conditions experienced early in life have profound consequences for vertebrate health, yet the molecular pathways linking developmental stress to aging and reduced lifespan remain poorly understood. Through a novel highly accurate epigenetic clock, developed from RRBS-based blood DNA methylation profiles, we show that experimental lifespan-reducing early-life stress rapidly accelerates epigenetic age in zebra finch chicks (Taeniopygia guttata). Corticosterone-treated 29-day-old chicks share differentially methylated loci with non-treated aged birds and cluster with 6-month-old birds. The transcriptional repressor ZBTB16 emerges as an epigenetically top age-correlated gene and is strongest affected by corticosterone. Elevated developmental corticosterone causes rapid epigenetic remodelling of metabolic pathways well-established in aging and longevity. Our results demonstrate epigenetic rewiring of the aging trajectory through conserved stress-survival mechanisms immediately following elevated early-life stress exposure.
]]></description>
<dc:creator><![CDATA[ Olova, N. N., Zhou, T., Boner, W., Gillespie, R., Ivimey-Cook, E. R., Marioni, R., Cunningham, E. J. A., Chandra, T., Little, T. J., Monaghan, P., Dominoni, D. M. ]]></dc:creator>
<dc:date>2026-10-02</dc:date>
<dc:identifier>doi:10.64898/2026.09.30.755600</dc:identifier>
<dc:title><![CDATA[Increased stress in early life epigenetically rewires pathways related to aging and longevity]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.09.30.755211v1?rss=1">
<title>
<![CDATA[
BMP6 coordinates dermal papilla and epithelial cell states for hair follicle engineering and regeneration 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.09.30.755211v1?rss=1
</link>
<description><![CDATA[
Human hair follicle engineering is hindered by the rapid loss of inductive competence in culture-expanded dermal papilla (DP) fibroblasts. Here we show that bone morphogenetic protein 6 (BMP6) maintains and restores DP-associated characteristics while promoting follicular epithelial differentiation by restricting keratinocyte (KC) proliferation and inducing hair follicle-associated marker expression. Human follicle transcriptomics further linked BMP activity to DP identity and follicular epithelial differentiation. Genetic mouse studies demonstrate that BMP6 in Sox2-positive DP cells contributes to normal anagen onset, progression, and maintenance. Gain- and loss-of-function studies in KC-DP organoids show that BMP6 promotes epithelial-mesenchymal organization and spatially patterned follicular structures. In vivo, topical BMP6 promotes anagen onset, whereas BMP6 overexpression restores the hair follicle-generating capacity of late-passage human DP fibroblasts. Together, these findings identify BMP6 as a compartment-dependent regulator that enhances human DP competence and promotes epithelial differentiation, supporting regenerative hair follicle formation and engineering with culture-expanded DP cells.
]]></description>
<dc:creator><![CDATA[ Siegfried, L. G., Zhou, L., Wang, J., Hahn, J. M., Dodson, C., Choi, Y. S., Babitt, J. L., Supp, D. M., Millar, S. E., Andl, T., Zhang, Y. ]]></dc:creator>
<dc:date>2026-10-02</dc:date>
<dc:identifier>doi:10.64898/2026.09.30.755211</dc:identifier>
<dc:title><![CDATA[BMP6 coordinates dermal papilla and epithelial cell states for hair follicle engineering and regeneration]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.09.30.754670v1?rss=1">
<title>
<![CDATA[
Creation of a High-Resolution, Continually Evolvable Lineage Tracer 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.09.30.754670v1?rss=1
</link>
<description><![CDATA[
Cellular diversity is required for the proper function of many tissues, including the retina, with its ~130 cell types.1-3 Previous lineage studies suggested that retinal progenitor cells (RPCs) generate cell diversity through biased cell divisions.4-9 However, the extent to which each progenitor cell contributes to diversity, and the overarching rules governing the lineages of the collection of progenitor cells, are unknown. While classic lineage tracing approaches including retroviral labeling4,6,10, dye injection11,12, and time-lapse microscopy13,14 were used to make the foundational insights regarding retinal lineages, they cannot be used to interrogate multigenerational lineages at scale. Here we describe the creation of an evolvable lineage tracing tool, "SCRIBBLE" for Sequential Combinatorial Recorder for Iterative Barcode-Based Lineage Evolution. SCRIBBLE uses prime editor to iteratively edit a barcode sequence while preserving the order of genesis of clonally related progeny. Through a series of rationally designed high-throughput screens and design optimizations, we identified novel sequences that support a high level of barcode editing and information content. Evaluation of SCRIBBLE in embryonic mouse retina recapitulated known lineages in retinal development, demonstrating that SCRIBBLE is capable of high-resolution lineage tracing in a complex tissue.
]]></description>
<dc:creator><![CDATA[ Delgado, R. N., Si, Y., Andersen, R. E., Lee, C., Bushnell, H. L., Doman, J. L., Pandey, S., Sousa, A. A., West, E. R., Dagotto, C. E., Liu, D. R., Cepko, C. L. ]]></dc:creator>
<dc:date>2026-10-02</dc:date>
<dc:identifier>doi:10.64898/2026.09.30.754670</dc:identifier>
<dc:title><![CDATA[Creation of a High-Resolution, Continually Evolvable Lineage Tracer]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-02</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.09.30.729488v1?rss=1">
<title>
<![CDATA[
Cerebral organoids recapitulate interneuron chain migration in the human cortex 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.09.30.729488v1?rss=1
</link>
<description><![CDATA[
The human brain is incomplete at birth, with streams of late-born interneurons migrating into the postnatal cortex. This process is absent in rodents, limiting mechanistic investigation to post-mortem tissue. Here, we show that human cerebral organoids cultured for over six months recapitulate postnatal interneuron migration, enabling its mechanistic and genetic dissection. Live imaging and mathematical modeling revealed that interneurons intrinsically migrate in chains, while astrocyte interactions promote stream organization. Spatial and single-cell transcriptomics identified a distinct molecular signature of human postnatal migratory streams enriched for neurodevelopmental disorder-associated genes. Perturbation of the autism-associated genes CNTN5 and FGF14 differentially disrupted chain organization and migration. Thus, long-term cerebral organoids enable mechanistic analysis of previously inaccessible aspects of postnatal human brain development and their contributions to neurodevelopmental disease.
]]></description>
<dc:creator><![CDATA[ Nagumo Wong, S., Noble, M. A., Fischer, M., Meyer, L., Novatchkova, M., Novakova, E., van der Heijden, D., Moya, L. B., Gonzalez-Granero, S., Garcia-Verdugo, J. M., Merino-Aceituno, S., Corsini, N. S., Knoblich, J. A. ]]></dc:creator>
<dc:date>2026-10-01</dc:date>
<dc:identifier>doi:10.64898/2026.09.30.729488</dc:identifier>
<dc:title><![CDATA[Cerebral organoids recapitulate interneuron chain migration in the human cortex]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://www.biorxiv.org/content/10.64898/2026.09.25.754262v1?rss=1">
<title>
<![CDATA[
Membrane progesterone receptors PAQR6 and PAQR8 in the ruminant uterus and ovary 
]]>
</title>
<link>
https://www.biorxiv.org/content/10.64898/2026.09.25.754262v1?rss=1
</link>
<description><![CDATA[
Progesterone governs the establishment and maintenance of pregnancy in ruminants, acting through the nuclear progesterone receptor (PGR) and, potentially, through membrane progesterone receptors (mPRs) of the PAQR family. The cellular distribution of mPRs in ruminant reproductive tissues, however, remains undefined. We generated and validated rabbit polyclonal antibodies against the intracellular C-terminal peptides of bovine PAQR6 (mPR{delta}) and PAQR8 (mPR{beta}), and used them, with quantitative PCR of the uterus and conceptus, to map these receptors in the ovine uterus and conceptus and in the bovine ovary. Both antisera showed high ELISA titer against their immunizing peptides, negligible preimmune reactivity, and complete loss of tissue signal after peptide pre-absorption. By qPCR, PAQR6, PAQR8 and PGR transcript levels did not change significantly across the peri-implantation period in either the conceptus or the endometrium; in contrast, the progesterone-responsive gene ZBTB16 increased markedly in the conceptus (up to ~45-fold by day 21, p < 0.05 at days 17, 19 and 21), whereas FKBP5 showed a numerical increase without reaching statistical significance. Both genes remained relatively stable in the endometrium, indicating conceptus-specific changes in progesterone-responsive gene expression. At the protein level, PAQR6 and PAQR8 localized to the luminal and glandular epithelium of the endometrium across the cycle and early pregnancy, and to follicular (granulosa) and luteal cells of the ovary. Dual immunofluorescence in the ovine endometrium showed that both PAQR6 and PAQR8 are enriched at the apical surface of the luminal epithelium and are spatially distinct from the basolateral adherens-junction marker E-cadherin. These results provide a protein-level map of PAQR6 and PAQR8 in the ruminant reproductive tract, identify the apical epithelial surface as a site of receptor enrichment, and show that the endometrial epithelium retains membrane progesterone receptors while progesterone-responsive gene expression changes dynamically in the conceptus during the peri-implantation period. The validated ruminant-reactive antibodies provide a resource for future functional studies.
]]></description>
<dc:creator><![CDATA[ Yang, H., Yamamoto, Y., Yamano, M., Matsuno, Y., Imakawa, K., Osakada, F., Ohno, H., Kondoh, E., Kimura, I., Nagaoka, K. ]]></dc:creator>
<dc:date>2026-10-01</dc:date>
<dc:identifier>doi:10.64898/2026.09.25.754262</dc:identifier>
<dc:title><![CDATA[Membrane progesterone receptors PAQR6 and PAQR8 in the ruminant uterus and ovary]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory</dc:publisher>
<prism:publicationDate>2026-10-01</prism:publicationDate>
<prism:section></prism:section>
</item>
</rdf:RDF>
