DevelopmentPub Date : 2025-10-15Epub Date: 2025-07-09DOI: 10.1242/dev.204483
Yuwei Pan, Shiyang Wang, Wuqi Yang, Xi Wu, Hanfu Zhang, Sujuan Du, Mingxin Zhang, Liyuan Hou, Maksim V Plikus, Jianwei Shuai, Cong Lv, Lu Yu, Zhengquan Yu
{"title":"Mesenchymal SLMAP coordinates with MST3 to govern gut elongation during development.","authors":"Yuwei Pan, Shiyang Wang, Wuqi Yang, Xi Wu, Hanfu Zhang, Sujuan Du, Mingxin Zhang, Liyuan Hou, Maksim V Plikus, Jianwei Shuai, Cong Lv, Lu Yu, Zhengquan Yu","doi":"10.1242/dev.204483","DOIUrl":"10.1242/dev.204483","url":null,"abstract":"<p><p>Developing gut in mice undergoes rapid elongation during late embryogenesis, yet significantly slows down after birth. The precise regulatory mechanism of this dynamic morphogenetic process remains unknown. By utilizing single-cell RNA-sequencing analysis, we show that YAP activity in intestinal fibroblasts is the major molecular contributor to gut elongation. To determine how mesenchymal YAP activity is controlled, we identified canonical sarcolemma membrane-associated protein (SLMAP) as its critical regulator during mouse embryonic gut morphogenesis. Deleting Slmap in gut mesenchyme impairs YAP activity, leading to a short gut and a significant decrease in intestinal epithelial cell proliferation. Mechanistically, SLMAP activates YAP by directly regulating MST3 kinase. Physiologically, MST3 levels prominently increase over the developmental time, reaching their peak on postnatal day (P)14, when gut elongation in mice slows down. Depleting Mst3 in mesenchyme results in increased gut length at P14 accompanied by enhanced YAP activity. Importantly, a short gut phenotype in mesenchyme-specific Slmap mutant mice is partially compensated for by concomitant deletion of mesenchymal Mst3. Taken together, our findings demonstrate that SLMAP interacts with MST3 kinase to regulate the mesenchymal YAP activity that governs dynamic gut elongation across embryonic and postnatal development.</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":"144301363","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 : 2025-10-15Epub Date: 2025-06-17DOI: 10.1242/dev.204952
{"title":"An interview with Mansi Srivastava.","authors":"","doi":"10.1242/dev.204952","DOIUrl":"https://doi.org/10.1242/dev.204952","url":null,"abstract":"<p><p>Mansi Srivastava is Professor of Organismic and Evolutionary Biology at Harvard University, USA, where her group has developed the three-banded panther worm (Hofstenia miamia) as a model system in which to study whole-body regeneration. This year, Mansi is a Guest Editor for Development's special issue on lifelong development, which highlights how developmental processes and pathways are used throughout animal lifespans. We last interviewed Mansi in 2022, so we caught up with her over Zoom to discuss the importance of studying development across the lifetime of an organism, how this relates to her own research, and why Hofstenia is the perfect model for studying the extent to which regeneration involves the recapitulation of developmental processes.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 20","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316177","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 : 2025-10-15Epub Date: 2025-06-20DOI: 10.1242/dev.204810
Evan W Craig, Erik C Black, Samantha Z Fernandes, Ahlan S Ferdous, Camille E A Goo, Sheridan M Sargent, Elgene J A Quitevis, Avery Angell Swearer, Nathaniel G Yee, Jimann Shin, Lilianna Solnica-Krezel, Jeffrey P Rasmussen
{"title":"Dendritic atoh1a+ cells serve as Merkel cell precursors during skin development and regeneration.","authors":"Evan W Craig, Erik C Black, Samantha Z Fernandes, Ahlan S Ferdous, Camille E A Goo, Sheridan M Sargent, Elgene J A Quitevis, Avery Angell Swearer, Nathaniel G Yee, Jimann Shin, Lilianna Solnica-Krezel, Jeffrey P Rasmussen","doi":"10.1242/dev.204810","DOIUrl":"10.1242/dev.204810","url":null,"abstract":"<p><p>Sensory cells often adopt specific morphologies that aid in the detection of external stimuli. Merkel cells encode gentle touch stimuli in vertebrate skin and adopt a reproducible shape characterized by spiky actin-rich microvilli that emanate from the cell surface. The mechanisms by which Merkel cells acquire this stereotyped morphology from keratinocyte progenitors are unknown. Here, we establish that dendritic Merkel cells (dMCs) express atonal homolog 1a (atoh1a), extend dynamic filopodial processes, and arise in transient waves during zebrafish skin development and regeneration. We find that dMCs share molecular similarities with both basal keratinocytes and Merkel cells, yet display mesenchymal-like behaviors, including local cell motility and proliferation within the epidermis. Furthermore, dMCs can directly adopt the mature, microvilliated Merkel cell morphology through substantial remodeling of the actin cytoskeleton. Loss of Ectodysplasin A signaling alters the morphology of dMCs and Merkel cells within specific skin regions. Our results show that dMCs represent an intermediate state in the Merkel cell maturation program and identify Ectodysplasin A signaling as a key regulator of Merkel cell morphology.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The transcription factor LHX2 suppresses astrocyte proliferation in the postnatal mammalian cerebral cortex.","authors":"Archana Iyer, Reanne Fronteiro, Prachi Bhatia, Sanjna Kumari, Amrita Singh, Jiafeng Zhou, Riccardo Bocchi, Rishikesh Narayanan, Shubha Tole","doi":"10.1242/dev.204358","DOIUrl":"10.1242/dev.204358","url":null,"abstract":"<p><p>In the developing cerebral cortex, astrocytes arise from progenitors in the ventricular and subventricular zones (V-SVZ), and also from local proliferation within the parenchyma. In the mouse neocortex, astrocytes that occupy upper layers (UL) versus deep layers (DL) are known to be distinct populations in terms of molecular and morphological features. The transcription factor LHX2 is expressed both in V-SVZ gliogenic progenitors and in differentiated astrocytes throughout development and into adulthood. Here, we show that loss of Lhx2 at birth results in an increased astrocyte proliferation in the UL but not the DL of the cortex in the first postnatal week. Consistent with this, transcriptomic signatures of UL astrocytes increase. By 3 months, Lhx2 mutant astrocytes display upregulation of GFAP, and transcriptomic signatures associated with 'reactive' astrocytes, in the absence of injury. These results demonstrate a role for Lhx2 in regulating proliferation and molecular features of cortical astrocytes.</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":"143998797","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 : 2025-10-15Epub 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 : 2025-10-15Epub Date: 2025-06-03DOI: 10.1242/dev.204610
Brady P Hammond, Sameera Zia, Eugene Hahn, Margarita Kapustina, Tristan Lange, Sarah Friesen, Rupali Manek, Kelly V Lee, Adrian Castellanos-Molina, Floriane Bretheau, Mark S Cembrowski, Bradley J Kerr, Steve Lacroix, Jason R Plemel
{"title":"CSF1R ligands promote microglial proliferation but are not the sole regulators of developmental microglial proliferation.","authors":"Brady P Hammond, Sameera Zia, Eugene Hahn, Margarita Kapustina, Tristan Lange, Sarah Friesen, Rupali Manek, Kelly V Lee, Adrian Castellanos-Molina, Floriane Bretheau, Mark S Cembrowski, Bradley J Kerr, Steve Lacroix, Jason R Plemel","doi":"10.1242/dev.204610","DOIUrl":"10.1242/dev.204610","url":null,"abstract":"<p><p>Microglia - the predominant immune cells of the brain and spinal cord - perform essential functions for the development and maintenance of the central nervous system, contingent upon the regulated developmental proliferation of microglia. However, the factor(s) that regulate microglial proliferation remain unclear. Here, we confirmed the timeline of developmental proliferation and used bioinformatics to identify potential signalling onto microglia in mouse from datasets collected at an age of high developmental microglial proliferation. Of the predicted factors, we found that colony stimulating factor 1 receptor (CSF1R) ligands boosted proliferation in vitro and were increasingly expressed in the brain across development with each displaying a distinct regional and temporal expression pattern. However, we did not observe a coincident alteration to CSF1R ligand levels in a model of abnormal developmental proliferation. Together, although CSF1R ligands can promote microglial proliferation in culture, their developmental expression patterns suggest that they function alongside other unknown factors to regulate developmental microglial proliferation.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-10-15Epub Date: 2025-07-11DOI: 10.1242/dev.204395
Dong Feng, Yanhan Dong, Yiran Song, Nicholas Yapundich, Yifang Xie, Brian Spurlock, Tingting Lyu, Landry Kuehn, Li Qian, Jiandong Liu
{"title":"Nr4a1 modulates inflammation and heart regeneration in zebrafish.","authors":"Dong Feng, Yanhan Dong, Yiran Song, Nicholas Yapundich, Yifang Xie, Brian Spurlock, Tingting Lyu, Landry Kuehn, Li Qian, Jiandong Liu","doi":"10.1242/dev.204395","DOIUrl":"10.1242/dev.204395","url":null,"abstract":"<p><p>Recent findings have highlighted the complex role of inflammation in zebrafish heart regeneration, demonstrating that although inflammation is essential for initiating transient fibrosis and tissue repair, chronic inflammation, and unresolved fibrosis, could impede full regenerative recovery. In this study, we identified the nuclear receptor Nr4a1 as a crucial regulator of this regenerative process in zebrafish. Loss of Nr4a1 function led to a prolonged and excessive inflammatory response, disrupted neutrophil migration, delayed fibrin clearance, and ultimately impaired heart regeneration. Transcriptome-wide RNA-seq analysis at different injury stages revealed molecular disruptions associated with dysregulated inflammation and fibrosis in nr4a1 mutants. Notably, partial inhibition of the pro-inflammatory cytokine Tnfα rescued heart regeneration in the nr4a1 mutants, highlighting the therapeutic potential of modulating inflammation. Our findings suggest that Nr4a1 plays a crucial role in orchestrating the immune response during heart regeneration and may serve as a valuable target for enhancing cardiac repair following injury.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-10-15Epub Date: 2025-06-17DOI: 10.1242/dev.204265
Berivan Temiz, Michael Meier, Megan J Wilson
{"title":"Single-cell transcriptomic profiling of the whole colony of Botrylloides diegensis: insights into tissue specialization and blastogenesis.","authors":"Berivan Temiz, Michael Meier, Megan J Wilson","doi":"10.1242/dev.204265","DOIUrl":"10.1242/dev.204265","url":null,"abstract":"<p><p>Botrylloides diegensis is a colonial ascidian that has been the focus of developmental, evolutionary and regeneration research. In this study, we performed single-cell RNA sequencing (scRNA-seq) of an entire B. diegensis colony, including zooids, buds and vascular tunics, to resolve cellular heterogeneity and to identify cell and tissue markers. We identified 29 major cell clusters within the colony and used in situ hybridization to examine the spatial expression of cluster marker genes. Numerous tissue types were identified at the molecular level, including blood cells and zooid tissues, such as the branchial epithelium, stomach and endostyle. Distinct cluster markers were identified for specific regions of the stomach epithelium, highlighting the specialization of these regions and the strength of using scRNA-seq to explore their functionality. Cell trajectory projections highlighted the early appearance of progenitor clusters, whereas more differentiated zooid-related tissues appeared later in the developmental path. This study provides a valuable resource for understanding the development, tissue function and regeneration of B. diegensis. It demonstrates the power of scRNA-seq to define cell types and tissues in complex colonial organisms.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-10-15Epub Date: 2025-07-30DOI: 10.1242/dev.204790
Amruta Tendolkar, Mayssa H Mokalled
{"title":"Mechanisms underpinning spontaneous spinal cord regeneration.","authors":"Amruta Tendolkar, Mayssa H Mokalled","doi":"10.1242/dev.204790","DOIUrl":"https://doi.org/10.1242/dev.204790","url":null,"abstract":"<p><p>Vertebrates exhibit a range of regenerative capacities following spinal cord injury. At one end of the spectrum are chief regenerators, including teleost fish and urodele amphibians. At the other end, most mammalian species exhibit limited repair and multicellular complications following spinal cord injury. Pro-regenerative immune, glial and neuronal injury responses underlie innate spinal cord repair in highly regenerative vertebrates. In many instances, fundamental mechanisms of spinal cord repair represent ancestral neuroprotection mechanisms that are conserved but become overwhelmed by anti-regenerative effects in mammals. Reflecting recent advances in the field, we review how fine-tuned immune responses, pro-regenerative glial cell reactivity and multimodal neuronal repair direct innate spinal cord repair.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 20","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741626","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 : 2025-08-01Epub Date: 2025-08-04DOI: 10.1242/dev.205038
{"title":"Pathway to Independence - an interview with Anzy Miller.","authors":"","doi":"10.1242/dev.205038","DOIUrl":"https://doi.org/10.1242/dev.205038","url":null,"abstract":"<p><p>Anzy Miller, former Sir Henry Wellcome Postdoctoral Fellow supported by Nancy Papalopulu (The University of Manchester, UK), is interested in the mechanisms involved in the generation of human pancreatic endocrine cells. Anzy is part of the 2025 cohort of fellows in Development's Pathway to Independence programme, which aims to support postdocs in obtaining their first faculty positions. We met with Anzy over Teams to learn more about her research interests at the intersection of developmental biology and mathematical modelling, as well as her advocacy for inclusivity and sustainability in scientific research.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 15","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774931","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}