DevelopmentPub Date : 2025-03-15Epub Date: 2025-03-24DOI: 10.1242/dev.204278
Claire S Simon, Woonyung Hur, Vidur Garg, Ying-Yi Kuo, Kathy K Niakan, Anna-Katerina Hadjantonakis
{"title":"ETV4 and ETV5 orchestrate FGF-mediated lineage specification and epiblast maturation during early mouse development.","authors":"Claire S Simon, Woonyung Hur, Vidur Garg, Ying-Yi Kuo, Kathy K Niakan, Anna-Katerina Hadjantonakis","doi":"10.1242/dev.204278","DOIUrl":"10.1242/dev.204278","url":null,"abstract":"<p><p>Cell fate decisions in early mammalian embryos are tightly regulated processes crucial for proper development. While FGF signalling plays key roles in early embryo patterning, its downstream effectors remain poorly understood. Our study demonstrates that the transcription factors Etv4 and Etv5 are crucial mediators of FGF signalling in cell lineage specification and maturation in mouse embryos. We show that loss of Etv5 compromises primitive endoderm formation at pre-implantation stages. Furthermore, Etv4 and Etv5 (Etv4/5) deficiency delays naïve pluripotency exit and epiblast maturation, leading to elevated NANOG and reduced OTX2 expression within the blastocyst epiblast. As a consequence of delayed pluripotency progression, Etv4/Etv5-deficient embryos exhibit anterior visceral endoderm migration defects post-implantation, a process essential for coordinated embryonic patterning and gastrulation initiation. Our results demonstrate the successive roles of these FGF signalling effectors in early lineage specification and embryonic body plan establishment, providing new insights into the molecular control of mammalian development.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499763","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 : 2025-03-15Epub Date: 2025-03-18DOI: 10.1242/dev.202666
Kai Wang, Ritsuko Suyama, Nanako Mizutani, Masaki Matsuo, Yu Peng, Masahide Seki, Yutaka Suzuki, Nicholas M Luscombe, Christelle Dantec, Patrick Lemaire, Atsushi Toyoda, Hiroki Nishida, Takeshi A Onuma
{"title":"Transcriptomes of a fast-developing chordate uncover drastic differences in transcription factors and localized maternal RNA composition compared with those of ascidians.","authors":"Kai Wang, Ritsuko Suyama, Nanako Mizutani, Masaki Matsuo, Yu Peng, Masahide Seki, Yutaka Suzuki, Nicholas M Luscombe, Christelle Dantec, Patrick Lemaire, Atsushi Toyoda, Hiroki Nishida, Takeshi A Onuma","doi":"10.1242/dev.202666","DOIUrl":"https://doi.org/10.1242/dev.202666","url":null,"abstract":"<p><p>The larvacean Oikopleura dioica is a fast-developing chordate because of its small number of cells (∼4500 in juveniles) and rapid development to complete morphogenesis by 10 h after fertilization. Strikingly, most of its blastomeres are restricted to give rise to a single cell-type by the 32-cell stage of embryogenesis, unlike cell fate determination at the 110-cell stage in ascidians. In this study, RNA-sequencing (RNA-seq) revealed non-canonical properties of O. dioica: (1) an initial zygotic gene expression of 950 genes at the 16- to 32-cell stage; (2) 25 transcription factors (TFs) are expressed in the 32-cell stage (fewer than half of the TFs underlying gene regulatory networks in ascidian embryogenesis were lost or not expressed); (3) five maternal mRNAs localized in the vegetal-posterior blastomeres in animal and vegetal hemispheres; and (4) three maternal mRNAs localized in the small vegetal pole region of unfertilized eggs. These observations indicate that this fast-developing chordate lacks the first phase of development in ascidians: fertilization-driven ooplasmic movements that drive postplasmic RNAs toward the vegetal pole. These data have been deposited in ANISEED (https://www.aniseed.fr/) as transcriptome resources.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656457","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 : 2025-03-15Epub Date: 2025-03-24DOI: 10.1242/dev.204311
Anna Nordin, Gianluca Zambanini, Mattias Enar Jonasson, Tamina Weiss, Yorick van de Grift, Pierfrancesco Pagella, Claudio Cantù
{"title":"Construction of an atlas of transcription factor binding during mouse development identifies popular regulatory regions.","authors":"Anna Nordin, Gianluca Zambanini, Mattias Enar Jonasson, Tamina Weiss, Yorick van de Grift, Pierfrancesco Pagella, Claudio Cantù","doi":"10.1242/dev.204311","DOIUrl":"10.1242/dev.204311","url":null,"abstract":"<p><p>Gene regulators physically associate with the genome, in a combinatorial fashion, to drive tissue-specific gene expression. Uncovering the genome-wide activity of all gene regulators across tissues is therefore needed to understand gene regulation during development. Here, we take a first step towards this goal. Using CUT&RUN, we systematically mapped genome-wide binding profiles of key transcription factors and co-factors that mediate ontogenetically relevant signaling pathways in select mouse tissues at two developmental stages. Computation of the datasets unveiled tissue- and time-specific activity for each gene regulator. We identified 'popular' regulatory regions that are bound by a multitude of regulators, which tend to be more evolutionarily conserved. Consistently, they lie near the transcription start site of genes for which dysregulation results in early embryonic lethality. Moreover, the human homologs of these regions are similarly bound by many gene regulators and are highly conserved, indicating a retained relevance for human development. This work constitutes a decisive step towards understanding how the genome is simultaneously read and used by gene regulators in a holistic fashion to drive embryonic development.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515068","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 : 2025-03-15Epub Date: 2025-03-26DOI: 10.1242/dev.204398
Anne Bourdais, Patricia Viard, Jenny Bormann, Côme Sesboüé, Daniel Guerrier, Nicole Therville, Julie Guillermet-Guibert, John Carroll, Guillaume Halet
{"title":"Distinct requirements for PI3K isoforms p110α and p110δ for PIP3 synthesis in mouse oocytes and early embryos.","authors":"Anne Bourdais, Patricia Viard, Jenny Bormann, Côme Sesboüé, Daniel Guerrier, Nicole Therville, Julie Guillermet-Guibert, John Carroll, Guillaume Halet","doi":"10.1242/dev.204398","DOIUrl":"10.1242/dev.204398","url":null,"abstract":"<p><p>The phosphoinositide 3-kinase (PI3K)/Akt pathway is thought to regulate key steps of mammalian oogenesis, such as dormant oocyte awakening during follicular activation, meiotic resumption and oocyte maturation. Supporting evidence is, however, indirect, as oocyte PI3K activation has never been formally demonstrated, and the PI3K isoforms involved have not been revealed. Here, we employed fluorescent PIP3 biosensors to characterize PI3K dynamics in mouse oocytes and we investigated the contribution of the PI3K isoform p110α by conditional genetic ablation. Prophase oocytes showed baseline PI3K/Akt activation that could be further stimulated by adding Kit ligand. Contrary to previous reports, maternal PI3K proved dispensable for oocyte maturation in vitro, yet it was required for PIP3 synthesis in early embryos. We further show that oocyte p110α is not essential for oogenesis and female fertility. Accordingly, our data suggest that Kit ligand activates isoform p110δ for PIP3 synthesis in oocytes. In contrast, constitutive PIP3 synthesis in early embryos is achieved by maternal p110α acting redundantly with p110δ. This study highlights the relevance of PIP3 biosensors in establishing the dynamics, mechanisms and roles of maternal PI3K signaling during mammalian oogenesis.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467310","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 : 2025-03-15Epub Date: 2025-03-31DOI: 10.1242/dev.204592
Dagmar Wilhelm, Aitana Perea-Gomez, Axel Newton, Marie-Christine Chaboissier
{"title":"Gonadal sex determination in vertebrates: rethinking established mechanisms.","authors":"Dagmar Wilhelm, Aitana Perea-Gomez, Axel Newton, Marie-Christine Chaboissier","doi":"10.1242/dev.204592","DOIUrl":"https://doi.org/10.1242/dev.204592","url":null,"abstract":"<p><p>Sex determination and differentiation are fundamental processes that are not only essential for fertility but also influence the development of many other organs, and hence, are important for species diversity and survival. In mammals, sex is determined by the inheritance of an X or a Y chromosome from the father. The Y chromosome harbours the testis-determining gene SRY, and it has long been thought that its absence is sufficient for ovarian development. Consequently, the ovarian pathway has been treated as a default pathway, in the sense that ovaries do not have or need a female-determining factor. Recently, a female-determining factor has been identified in mouse as the master regulator of ovarian development. Interestingly, this scenario was predicted as early as 1983. In this Review, we discuss the model predicted in 1983, how the mechanisms and genes currently known to be important for sex determination and differentiation in mammals have changed or supported this model, and finally, reflect on what these findings might mean for sex determination in other vertebrates.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751156","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 : 2025-03-07DOI: 10.1242/dev.204513
Rannyele P Ribeiro, Ryan W Null, B Duygu Özpolat
{"title":"Sex-biased gene expression precedes sexual dimorphism in the agonadal annelid Platynereis dumerilii.","authors":"Rannyele P Ribeiro, Ryan W Null, B Duygu Özpolat","doi":"10.1242/dev.204513","DOIUrl":"10.1242/dev.204513","url":null,"abstract":"<p><p>Gametogenesis is the process by which germ cells differentiate into mature sperm and oocytes, cells essential for sexual reproduction. The sex-specific molecular programs that drive spermatogenesis and oogenesis can also serve as sex identification markers. Platynereis dumerilii is a research organism that has been studied in many areas of developmental biology. However, investigations often disregard sex, as P. dumerilii juveniles lack sexual dimorphism. The molecular mechanisms of gametogenesis in the segmented worm P. dumerilii are also largely unknown. In this study, we used RNA sequencing to investigate the transcriptomic profiles of gametogenesis in P. dumerilii juveniles. Our analysis revealed that sex-biased gene expression becomes increasingly pronounced during the advanced developmental stages, as worms approach maturation. We identified conserved genes associated with spermatogenesis, such as dmrt1, and with oogenesis, such as a novel gene psmt. Additionally, putative long non-coding RNAs were upregulated in both male and female gametogenic programs. This study provides a foundational resource for germ cell research in P. dumerilii, markers for sex identification, and offers comparative data to enhance our understanding of the evolution of gametogenesis mechanisms across species.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604227","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 : 2025-03-01Epub Date: 2025-03-14DOI: 10.1242/dev.204624
Eliana Nehme, Amitesh Panda, Isabelle Migeotte, Vincent Pasque
{"title":"Extra-embryonic mesoderm during development and in in vitro models.","authors":"Eliana Nehme, Amitesh Panda, Isabelle Migeotte, Vincent Pasque","doi":"10.1242/dev.204624","DOIUrl":"10.1242/dev.204624","url":null,"abstract":"<p><p>Extra-embryonic tissues provide protection and nutrition in vertebrates, as well as a connection to the maternal tissues in mammals. The extra-embryonic mesoderm is an essential and understudied germ layer present in amniotes. It is involved in hematopoiesis, as well as in the formation of extra-embryonic structures such as the amnion, umbilical cord and placenta. The origin and specification of extra-embryonic mesoderm are not entirely conserved across species, and the molecular mechanisms governing its formation and function are not fully understood. This Review begins with an overview of the embryonic origin and function of extra-embryonic mesoderm in vertebrates from in vivo studies. We then compare in vitro models that generate extra-embryonic mesoderm-like cells. Finally, we discuss how insights from studying both embryos and in vitro systems can aid in designing even more advanced stem cell-based embryo models.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623932","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 : 2025-03-01Epub Date: 2025-03-12DOI: 10.1242/dev.204555
Christopher De Bono, Yichi Xu, Samina Kausar, Marine Herbane, Camille Humbert, Sevda Rafatov, Chantal Missirian, Mathias Moreno, Weiyang Shi, Yorick Gitton, Alberto Lombardini, Ivo Vanzetta, Séverine Mazaud-Guittot, Alain Chédotal, Anaïs Baudot, Stéphane Zaffran, Heather C Etchevers
{"title":"Multi-modal refinement of the human heart atlas during the first gestational trimester.","authors":"Christopher De Bono, Yichi Xu, Samina Kausar, Marine Herbane, Camille Humbert, Sevda Rafatov, Chantal Missirian, Mathias Moreno, Weiyang Shi, Yorick Gitton, Alberto Lombardini, Ivo Vanzetta, Séverine Mazaud-Guittot, Alain Chédotal, Anaïs Baudot, Stéphane Zaffran, Heather C Etchevers","doi":"10.1242/dev.204555","DOIUrl":"10.1242/dev.204555","url":null,"abstract":"<p><p>Forty first-trimester human hearts were studied to lay groundwork for further studies of the mechanisms underlying congenital heart defects. We first sampled 49,227 cardiac nuclei from three fetuses at 8.6, 9.0, and 10.7 post-conceptional weeks (pcw) for single-nucleus RNA sequencing, enabling the distinction of six classes comprising 21 cell types. Improved resolution led to the identification of previously unappreciated cardiomyocyte populations and minority autonomic and lymphatic endothelial transcriptomes, among others. After integration with 5-7 pcw heart single-cell RNA-sequencing data, we identified a human cardiomyofibroblast progenitor preceding the diversification of cardiomyocyte and stromal lineages. Spatial transcriptomic analysis (six Visium sections from two additional hearts) was aided by deconvolution, and key spatial markers validated on sectioned and whole hearts in two- and three-dimensional space and over time. Altogether, anatomical-positional features, including innervation, conduction and subdomains of the atrioventricular septum, translate latent molecular identity into specialized cardiac functions. This atlas adds unprecedented spatial and temporal resolution to the characterization of human-specific aspects of early heart formation.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381787","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 : 2025-03-01Epub Date: 2025-03-11DOI: 10.1242/dev.204728
{"title":"The people behind the papers - Juan Yang and Xuanmao Chen.","authors":"","doi":"10.1242/dev.204728","DOIUrl":"https://doi.org/10.1242/dev.204728","url":null,"abstract":"<p><p>In mammalian embryos, brains develop from the inside out, with younger neurons moving to the outer layers in a process called radial migration. A new paper in Development finds that, during postnatal development, some of the neurons in the outer layers of the brain undergo a 'reverse movement', repositioning themselves by moving in the opposite direction to the initial radial migration. To learn more about the story behind the paper, we caught up with first author Juan Yang and corresponding author Xuanmao Chen, Associate Professor of Neurobiology at the University of New Hampshire (UNH), USA.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604186","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 : 2025-03-01Epub Date: 2025-03-07DOI: 10.1242/dev.204501
Ling S Loh, Kyle A DeMarr, Martina Tsimba, Christa Heryanto, Alejandro Berrio, Nipam H Patel, Arnaud Martin, W Owen McMillan, Gregory A Wray, Joseph J Hanly
{"title":"Lepidopteran scale cells derive from sensory organ precursors through a canonical lineage.","authors":"Ling S Loh, Kyle A DeMarr, Martina Tsimba, Christa Heryanto, Alejandro Berrio, Nipam H Patel, Arnaud Martin, W Owen McMillan, Gregory A Wray, Joseph J Hanly","doi":"10.1242/dev.204501","DOIUrl":"10.1242/dev.204501","url":null,"abstract":"<p><p>The success of butterflies and moths is tightly linked to the origin of scales within the group. A long-standing hypothesis postulates that scales are homologous to the well-described mechanosensory bristles found in the fruit fly Drosophila melanogaster, as both derive from an epithelial precursor. Previous histological and candidate gene approaches identified parallels in genes involved in scale and bristle development. Here, we provide developmental and transcriptomic evidence that the differentiation of lepidopteran scales derives from the sensory organ precursor (SOP). Live imaging in lepidopteran pupae shows that SOP cells undergo two asymmetric divisions that first abrogate the neurogenic lineage, and then lead to a differentiated scale precursor and its associated socket cell. Single-nucleus RNA sequencing using early pupal wings revealed differential gene expression patterns that mirror SOP development, suggesting a shared developmental program. Additionally, we recovered a newly associated gene, the transcription factor pdm3, involved in the proper differentiation of butterfly wing scales. Altogether, these data open up avenues for understanding scale type specification and development, and illustrate how single-cell transcriptomics provide a powerful platform for understanding evolution of cell types.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572540","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}