DevelopmentPub Date : 2025-10-15Epub Date: 2025-03-27DOI: 10.1242/dev.204244
Andre M Xavier, Qianyu Lin, Chris J Kang, Lucas Cheadle
{"title":"A single-cell transcriptomic atlas of sensory-dependent gene expression in developing mouse visual cortex.","authors":"Andre M Xavier, Qianyu Lin, Chris J Kang, Lucas Cheadle","doi":"10.1242/dev.204244","DOIUrl":"10.1242/dev.204244","url":null,"abstract":"<p><p>Sensory experience drives the maturation of neural circuits during postnatal brain development through molecular mechanisms that remain to be fully elucidated. One likely mechanism involves the sensory-dependent expression of genes that encode direct mediators of circuit remodeling within developing cells. To identify potential drivers of sensory-dependent synaptic development, we generated a single-nucleus RNA sequencing dataset describing the transcriptional responses of cells in the mouse visual cortex to sensory deprivation or to stimulation during a developmental window when visual input is necessary for circuit refinement. We sequenced 118,529 nuclei across 16 neuronal and non-neuronal cell types isolated from control, sensory deprived and sensory stimulated mice, identifying 1268 sensory-induced genes within the developing brain. While experience elicited transcriptomic changes in all cell types, excitatory neurons in layer 2/3 exhibited the most robust changes, and the sensory-induced genes in these cells are poised to strengthen synapse-to-nucleus crosstalk and to promote cell type-specific axon guidance pathways. Altogether, we expect this dataset to significantly broaden our understanding of the molecular mechanisms through which sensory experience shapes neural circuit wiring in the developing brain.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-05-16DOI: 10.1242/dev.204694
Cole R Julick, Nattapon Thanintorn, Hongtao Zhang, Yonit Tsatskis, Megan Glaeser, Yi Qu, Jannette Rusch, Helen McNeill
{"title":"Regulation of Hippo signaling and planar cell polarity via distinct regions of the Fat intracellular domain.","authors":"Cole R Julick, Nattapon Thanintorn, Hongtao Zhang, Yonit Tsatskis, Megan Glaeser, Yi Qu, Jannette Rusch, Helen McNeill","doi":"10.1242/dev.204694","DOIUrl":"https://doi.org/10.1242/dev.204694","url":null,"abstract":"<p><p>The large Drosophila protocadherin Fat (Ft) is a receptor for signal transduction pathways that control growth (Hippo signaling), planar cell polarity (PCP), metabolism and the proximodistal patterning of appendages. The intracellular domain (ICD) of Ft is crucial in implementing its biological functions. Six regions of high conservation (named A-F) within the ICD have been identified, as well as distinct regions mediating Hippo pathway activity that have been functionally characterized via transgenic expression rescue assays. Here, we make targeted deletions of these highly conserved residues and the putative Hippo- and PCP-regulating domains of endogenous Ft using CRISPR/Cas9. Through transcriptomic, developmental, and phenotypic analyses, we show that different regions of Ft contribute uniquely to chromatin dynamics, tissue morphogenesis, PCP and metabolic regulation. We also demonstrate that different regions of Ft regulate growth in opposite directions, with regions B and F promoting growth and region D inhibiting growth. Strikingly, conserved regions D and F are key regulators of Ft's function in Hippo activity- exhibiting opposing effects on Hippo pathway modulation- and of the conserved regions, D is the main regulator of PCP.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-05-16DOI: 10.1242/dev.204505
Sarah S Soliman, Devan H Shah, Hana El-Samad, Zara Y Weinberg
{"title":"Small molecule and cell contact-inducible systems for controlling expression and differentiation in mouse embryonic stem cells.","authors":"Sarah S Soliman, Devan H Shah, Hana El-Samad, Zara Y Weinberg","doi":"10.1242/dev.204505","DOIUrl":"https://doi.org/10.1242/dev.204505","url":null,"abstract":"<p><p>Synthetic developmental biology uses engineering approaches to understand multicellularity with goals ranging from recapitulating development to building synthetic organisms. Current approaches include engineering multicellular patterning, controlling differentiation, and implementing cooperative cellular behaviors in model systems. Synthetic biology enables these pursuits by providing tools to control cell behavior. Mouse embryonic stem cells (mESCs) offer a well-studied and genetically tractable pluripotent model for pursuing synthetic development questions. However, there is minimal characterization of existing synthetic biology tools in mESCs. Here, we characterize three small molecule and two cell contact-inducible systems for gene expression in and differentiation of mESCs. We show that small molecule and cell-contact inducible systems work reliably and efficiently for controlling expression of arbitrary genetic payloads. We identify how these systems function differently across model differentiations. Furthermore, we show that these systems can drive direct differentiation of mESCs into neurons. Each of these systems can be used on their own or in combination, opening many possibilities for studying developmental principles with high precision.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-05-15Epub Date: 2025-05-16DOI: 10.1242/dev.204391
Katherine V Clayworth, Vanessa J Auld
{"title":"Dystroglycan mediates polarized deposition of laminin and axon ensheathment by wrapping glia.","authors":"Katherine V Clayworth, Vanessa J Auld","doi":"10.1242/dev.204391","DOIUrl":"10.1242/dev.204391","url":null,"abstract":"<p><p>The Drosophila peripheral nerve contains multiple layers of glial cells and an overlying extracellular matrix, which together support neuronal survival and function. The innermost glial layer, the wrapping glia (WG), ensheathes axons and facilitates action potential conduction. Recent work has identified involvement of laminin, a heterotrimeric extracellular matrix protein complex in WG development. However, the localization and function of laminin in the WG remains poorly understood. Here, we found that the α subunit, Laminin A (LanA), is dynamically expressed by WG, and loss of LanA results in a reduction in WG-axon contact. The deposition of LanA by WG is concentrated between WG and axons and is deposited preferentially around motor axons versus sensory axons. We identified Crag, a GDP-GTP exchange protein, as a factor that controls LanA deposition. We found that Dystroglycan also controls LanA deposition by the WG, and that both Dystroglycan and Dystrophin are present and necessary for WG ensheathment of axons. Thus, WG contain the highly conserved Dystroglycan/Dystrophin complex, which not only associates with deposited laminin but is necessary for the polarized deposition of laminin and the correct ensheathment of peripheral nerve axons.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-05-15Epub Date: 2025-05-16DOI: 10.1242/dev.204258
Cristina M Ostalé, Natalia Azpiazu, Ana Peropadre, Mercedes Martín, Mireya Ruiz-Losada, Ana López-Varea, Rebecca R Viales, Charles Girardot, Eileen E M Furlong, Jose F de Celis
{"title":"A function of Spalt proteins in heterochromatin organization and maintenance of genomic DNA integrity.","authors":"Cristina M Ostalé, Natalia Azpiazu, Ana Peropadre, Mercedes Martín, Mireya Ruiz-Losada, Ana López-Varea, Rebecca R Viales, Charles Girardot, Eileen E M Furlong, Jose F de Celis","doi":"10.1242/dev.204258","DOIUrl":"10.1242/dev.204258","url":null,"abstract":"<p><p>The conserved Spalt proteins regulate gene expression and cell fate choices during multicellular development, generally acting as transcriptional repressors in different gene regulatory networks. In addition to their roles as DNA sequence-specific transcription factors, Spalt proteins show a consistent localization to heterochromatic regions. Vertebrate Spalt-like proteins can act through the nucleosome remodeling and deacetylase complex to promote closing of open chromatin domains, but their activities also rely on interactions with DNA methyltransferases or with the lysine-specific histone demethylase LSD1, suggesting that they participate in multiple regulatory mechanisms. Here, we describe several consequences of loss of Spalt function in Drosophila cells, including changes in chromatin accessibility, generation of DNA damage, alterations in the localization of chromosomes within the nucleus in the salivary glands and misexpression of transposable elements. We suggest that these effects are related to roles of Spalt proteins in the regulation of heterochromatin formation and chromatin organization. We propose that Drosophila Spalt proteins have two complementary functions, acting as sequence-specific transcriptional repressors on specific target genes and regulating more global gene silencing through the generation or maintenance of heterochromatic domains.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-05-15DOI: 10.1242/dev.204870
Yonit Maroudas-Sacks, Marc Trani Bustos, Jesse V Veenvliet
{"title":"In preprints: exploring developmental robustness and timing with gastruloids.","authors":"Yonit Maroudas-Sacks, Marc Trani Bustos, Jesse V Veenvliet","doi":"10.1242/dev.204870","DOIUrl":"https://doi.org/10.1242/dev.204870","url":null,"abstract":"","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 10","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-05-15Epub Date: 2025-05-14DOI: 10.1242/dev.204884
Alessandro Bonfini, Peter Nagy, Nicolas Buchon
{"title":"In preprints: are microbes the architects of animal bodies?","authors":"Alessandro Bonfini, Peter Nagy, Nicolas Buchon","doi":"10.1242/dev.204884","DOIUrl":"https://doi.org/10.1242/dev.204884","url":null,"abstract":"","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 10","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-05-15DOI: 10.1242/dev.204277
Eleanor Zagoren, Nicolas Dias, Anderson K Santos, Zachary D Smith, Nadia A Ameen, Kaelyn Sumigray
{"title":"Evidence of secondary Notch signaling within the rat small intestine.","authors":"Eleanor Zagoren, Nicolas Dias, Anderson K Santos, Zachary D Smith, Nadia A Ameen, Kaelyn Sumigray","doi":"10.1242/dev.204277","DOIUrl":"https://doi.org/10.1242/dev.204277","url":null,"abstract":"<p><p>The small intestine is well known for its nutrient-absorbing enterocytes; yet equally critical for homeostasis is a diverse set of secretory cells, all presumed to originate from the same intestinal stem cell. Despite their major roles in intestinal function and health, understanding how the full spectrum of secretory cell types arises remains a longstanding challenge, largely due to their comparative rarity. Here, we investigate the specification of a rare population of small intestinal epithelial cells found in rats and humans but not mice: CFTR High Expressers (CHEs). Using pseudotime trajectory analysis of single-cell RNA-seq data from rat jejunum, we provide evidence that CHEs are specified along the secretory lineage and appear to employ a second wave of Notch-based signaling to distinguish themselves from other secretory cells. We validate the transcription factors directing these cells from crypt progenitors and demonstrate that Notch signaling is necessary to induce CHE fate in vivo and in vitro. Our findings suggest that Notch reactivation along the secretory lineage specifies CHEs, which may help regulate luminal pH and have direct relevance in cystic fibrosis pathophysiology.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-05-15DOI: 10.1242/dev.204901
{"title":"An interview with Helen Skaer.","authors":"","doi":"10.1242/dev.204901","DOIUrl":"https://doi.org/10.1242/dev.204901","url":null,"abstract":"<p><p>Helen Skaer is an Emeritus Professor of Developmental Biology at the University of Cambridge. Using Drosophila as her model organism, her research has provided insight into the development of the renal system. In recognition of this work, she was awarded the 2025 British Society for Developmental Biology's (BSDB) Waddington Medal, which recognises outstanding individuals who have made major contributions to UK Developmental Biology. Helen gave her award lecture at the Biologists @ 100 conference in Liverpool. The conference was organised to celebrate 100 years of The Company of Biologists, and it incorporated the BSDB's Spring Meeting. The week following her lecture, Helen visited The Company of Biologists office to tell us more about her research and what this award means to her.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 10","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-05-12DOI: 10.1242/dev.204361
Silvio A Traba, Lucas Bacigalupo, Daniella Fradin, Irene Talon, Ana C Heidenreich, Daniele Muraro, Jose Garcia-Bernardo, Christopher Gribben, Fatima Lugtu, Juan Ignacio Burgos, Agustín Romero, Mariya Chhatriwala, Adali Pecci, Ludovic Vallier, Santiago A Rodríguez-Seguí
{"title":"Endogenous glucocorticoid receptor activation modulates early-stage cell differentiation in pancreatic progenitors of mice and humans.","authors":"Silvio A Traba, Lucas Bacigalupo, Daniella Fradin, Irene Talon, Ana C Heidenreich, Daniele Muraro, Jose Garcia-Bernardo, Christopher Gribben, Fatima Lugtu, Juan Ignacio Burgos, Agustín Romero, Mariya Chhatriwala, Adali Pecci, Ludovic Vallier, Santiago A Rodríguez-Seguí","doi":"10.1242/dev.204361","DOIUrl":"https://doi.org/10.1242/dev.204361","url":null,"abstract":"<p><p>Understanding pancreatic development is instrumental to diabetes research and β-cell replacement therapies. Here, we investigate Glucocorticoid Receptor (GR) signaling during early pancreas development in mice and humans. Previous reports suggest that glucocorticoids do not play a significant role in mouse pancreas development before the second transition. In this study, we demonstrate that, under physiological conditions, the GR is selectively active in mouse pro-acinar and early endocrine cells from E11.5, silenced in bipotent progenitors, and reactivated during endocrine commitment. In mouse pancreatic explants, ectopic GR activation globally promotes acinar fate. Surprisingly, GR activation in human in vitro-derived multipotent pancreatic progenitors steers lineage commitment toward a bipotent/endocrine trajectory and upregulates novel genes whose expression profiles resemble those of SOX9 and HES1 during human embryonic pancreatic bipotential and endocrine progenitor fate choice. Our combined epigenomic and single-cell transcriptomic analyses suggest that these novel marker genes may play important roles in human pancreas development. Taken together, our findings position the GR pathway as an endogenous developmental modulator of early-stage pancreatic progenitor cell differentiation and provide insights into the underlying transcriptional mechanisms involved.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}