DevelopmentPub Date : 2025-01-15Epub Date: 2025-01-16DOI: 10.1242/dev.203033
Linh T Trinh, Ryan R Finnel, Anna B Osipovich, Jessica R Musselman, Leesa L Sampson, Christopher V E Wright, Mark A Magnuson
{"title":"Positive autoregulation of Sox17 is necessary for gallbladder and extrahepatic bile duct formation.","authors":"Linh T Trinh, Ryan R Finnel, Anna B Osipovich, Jessica R Musselman, Leesa L Sampson, Christopher V E Wright, Mark A Magnuson","doi":"10.1242/dev.203033","DOIUrl":"10.1242/dev.203033","url":null,"abstract":"<p><p>Expression of SRY-box transcription factor 17 (Sox17) in the endodermal region caudal to the hepatic diverticulum during late gastrulation is necessary for hepato-pancreato-biliary system formation. Analysis of an allelic series of promoter-proximal mutations near the transcription start site (TSS) 2 of Sox17 in mouse has revealed that gallbladder (GB) and extrahepatic bile duct (EHBD) development is exquisitely sensitive to Sox17 expression levels. Deletion of a SOX17-binding cis-regulatory element in the TSS2 promoter impairs GB and EHBD development by reducing outgrowth of the nascent biliary bud. These findings reveal the existence of a SOX17-dependent autoregulatory loop that drives Sox17 expression above a critical threshold concentration necessary for GB and EHBD development to occur, and that minor impairments in Sox17 gene expression are sufficient to impair the expression of SOX17-regulated genes in the nascent GB and EHBD system, impairing or preventing development.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913935","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 : 2025-01-15Epub Date: 2025-02-04DOI: 10.1242/dev.204387
João E Carvalho, Maxence Burtin, Olivier Detournay, Aldine R Amiel, Eric Röttinger
{"title":"Optimized husbandry and targeted gene-editing for the cnidarian Nematostella vectensis.","authors":"João E Carvalho, Maxence Burtin, Olivier Detournay, Aldine R Amiel, Eric Röttinger","doi":"10.1242/dev.204387","DOIUrl":"10.1242/dev.204387","url":null,"abstract":"<p><p>Optimized laboratory conditions for research models are crucial for the success of scientific projects. This includes controlling the entire life cycle, having access to all developmental stages and maintaining stable physiological conditions. Reducing the life cycle of a research model can also enhance the access to biological material and speed up genetic tool development. Thus, we optimized the rearing conditions for the sea anemone Nematostella vectensis, a cnidarian research model, to study embryonic and post-metamorphic processes, such as regeneration. We adopted a semi-automated aquaculture system for N. vectensis and developed a dietary protocol optimized for the different life stages. Thereby, we increased spawning efficiencies, juvenile growth and survival rates, and considerably reduced the overall life cycle down to 2 months. To further improve the obtention of CRISPR-Cas9 mutants, we optimized the design of sgRNAs leading to full knockout animals in F0 polyps using a single sgRNA. Finally, we show that NHEJ-mediated transgene insertion is possible in N. vectensis. In summary, our study provides additional resources for the scientific community that uses or plans to use N. vectensis as a research model.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946429","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 : 2025-01-15Epub Date: 2025-02-03DOI: 10.1242/dev.204645
{"title":"An interview with Sarah Bray.","authors":"","doi":"10.1242/dev.204645","DOIUrl":"https://doi.org/10.1242/dev.204645","url":null,"abstract":"<p><p>Sarah Bray is a Professor of Developmental Biology and the Joint Head of the Department of Physiology, Development and Neuroscience at the University of Cambridge, UK. In 2023, Sarah became the Chair of The Company of Biologists' Board of Directors. As the Company marks its 100-year anniversary in 2025, we met with Sarah to learn more about her early association with the Company, her responsibilities as the Chair of the Company's Board of Directors, the philosophy underlying the Company's longevity and our 100-year anniversary celebrations.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122430","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 : 2025-01-15Epub Date: 2025-02-04DOI: 10.1242/dev.202865
Valentyna Kostiuk, Rakib Kabir, Kaitlin Levangie, Stefany Empke, Kimberly Morgan, Nick D L Owens, C Patrick Lusk, Mustafa K Khokha
{"title":"Nup107 contributes to the maternal-to-zygotic transition by preventing the premature nuclear export of pri-miR427.","authors":"Valentyna Kostiuk, Rakib Kabir, Kaitlin Levangie, Stefany Empke, Kimberly Morgan, Nick D L Owens, C Patrick Lusk, Mustafa K Khokha","doi":"10.1242/dev.202865","DOIUrl":"10.1242/dev.202865","url":null,"abstract":"<p><p>Emerging evidence suggests that the nuclear pore complex can have unique compositions and distinct nucleoporin functions in different cells. Here, we show that Nup107, a key component of the NPC scaffold, varies in expression over development: it is expressed at higher levels in the blastula compared to the gastrula, suggesting a crucial role before gastrulation in Xenopus. We find that depletion of Nup107 affects the differentiation of the early germ layers leading to an expansion of the ectoderm at the expense of endoderm and mesoderm. By analyzing an RNA-sequencing time course, we observed that depletion of Nup107 affects the maternal-zygotic transition by delaying the degradation of maternal transcripts that occurs as zygotic transcription begins. The transcripts are enriched in recognition sites for miR427, a conserved microRNA that destabilizes maternal transcripts including REST, which encodes a Kruppel-type zinc-finger transcription factor that we demonstrate is crucial for ectodermal cell fates. Mechanistically, we show that Nup107 is required to prevent the premature export of pri-miR427 transcript before processing. Nup107 depletion leads to the reduced production of mature miR427 and maternal transcript stabilization. We conclude that high levels of Nup107 in the early embryo are crucial for the nuclear retention and subsequent processing of pri-miR427 transcripts that is required for timely maternal RNA clearance to enable gastrulation.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946428","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":"Abnormal H3K27me3 underlies degenerative spermatogonial stem cells in cryptorchid testis.","authors":"Kazushige Kuroha, Ivana Dočkal, Uroš Radović, Kuniko Nakajima, Ikue Hoshi, Shion Matsuda, Noriko Kojitani, Kazuyuki Ohbo, Shin-Ichi Tomizawa","doi":"10.1242/dev.204239","DOIUrl":"10.1242/dev.204239","url":null,"abstract":"<p><p>Cryptorchidism is the most frequent congenital defect in newborn males characterized by the absence of the testis from the scrotum. Approximately 90% of individuals with untreated bilateral cryptorchidism exhibit azoospermia due to defective spermatogenesis in the affected testis. Although abnormal spermatogonial stem cell maintenance or differentiation is suggested to cause germ cell degeneration in the cryptorchid testis, the underlying molecular mechanisms remain unclear. Here, we profiled spermatogonial epigenetic landscapes using surgically induced cryptorchid testis in the mouse. We show that cryptorchidism leads to alterations in local, but not global, H3K27me3 and H3K9me3 in undifferentiated spermatogonia. Of these, the loss of H3K27me3 was correlated with activation of developmental and proapoptotic pathway genes that are repressed by the polycomb machinery in germ cells. Cryptorchid spermatogonia exhibit an increase of the H3K27me3 demethylases KDM6A and KMD6B. Furthermore, we reveal that an increased temperature leads to Kdm6a/b upregulation in germline stem cells cultured in vitro. Thus, our study suggests that temperature-dependent histone demethylation may induce mRNA dysregulation due to the partial loss of H3K27me3 in spermatogonia.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913931","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":"Canonical Wnt signalling from the area opaca induces and maintains the marginal zone in pre-primitive-streak stage chick embryos.","authors":"Yara Fadaili, Hui-Chun Lu, Hyung Chul Lee, Amra Ryazapova, Claudio D Stern","doi":"10.1242/dev.204350","DOIUrl":"10.1242/dev.204350","url":null,"abstract":"<p><p>In chick embryos before primitive streak formation, the outermost extra-embryonic region, known as the area opaca (AO), was generally thought to act only by providing nutrients and mechanical support to the embryo. Immediately internal to the AO is a ring of epiblast called the marginal zone (MZ), separating the former from the inner area pellucida (AP) epiblast. The MZ does not contribute cells to any part of the embryo but is involved in determining the position of primitive streak formation from the adjacent AP epiblast. Recently, it was discovered that the AO can induce an MZ from AP epiblast. Here, we explore the nature of this inductive signal. We find that WNT8C is highly expressed in the AO, whereas canonical Wnt pathway targets are enriched in the MZ, along with strong nuclear β-catenin localization. Using isolation and recombination experiments combined with gain- and loss-of-function by exogenous chemical modulators of the pathway, we reveal that Wnt signalling is essential for induction and maintenance of the MZ, as well as sufficient to induce MZ properties in AP epiblast. We propose that canonical Wnt signalling is responsible for induction of the MZ by the area opaca.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970058","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 : 2025-01-15Epub Date: 2025-01-16DOI: 10.1242/dev.204382
Izumi Oda, Yutaka Satou
{"title":"A master regulatory loop that activates genes in a temporally coordinated manner in muscle cells of ascidian embryos.","authors":"Izumi Oda, Yutaka Satou","doi":"10.1242/dev.204382","DOIUrl":"10.1242/dev.204382","url":null,"abstract":"<p><p>Ascidian larval muscle cells present a classic example of autonomous development. A regulatory mechanism for these cells has been extensively investigated, and the regulatory gene circuit has been documented from maternal factors to a muscle-specific gene. In the present study, we comprehensively identified genes expressed specifically in ascidian muscle cells, and found that all of them are under control of a positive regulatory loop of Tbx6-r.b and Mrf, the core circuit identified previously. We also found that several transcription factors under control of the Tbx6-r.b/Mrf regulatory loop exhibited various temporal expression profiles, which are probably important for creating functional muscle cells. These results, together with results of previous studies, provide an exhaustive view of the regulatory system enabling autonomous development of ascidian larval muscle cells. It shows that the Tbx6-r.b/Mrf regulatory loop, but not a single gene, serves a 'master' regulatory function. This master regulatory loop not only controls spatial gene expression patterns, but also governs temporal expression patterns in ascidian muscle cells.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913928","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 : 2025-01-15Epub Date: 2025-02-04DOI: 10.1242/dev.204648
{"title":"The people behind the papers - Valentyna Kostiuk and Mustafa Khokha.","authors":"","doi":"10.1242/dev.204648","DOIUrl":"https://doi.org/10.1242/dev.204648","url":null,"abstract":"<p><p>The nuclear pore has been thought to have a consistent function during development, although its composition can vary. In this issue, Valentyna Kostiuk and colleagues reveal a context-specific role of a nucleoporin, Nup107, in the maternal-to-zygotic transition. We caught up with first author Valentyna Kostiuk and corresponding author Mustafa Khokha, Professor and Principal Investigator at Yale School of Medicine, USA, to learn more.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122523","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 : 2025-01-15Epub Date: 2025-01-16DOI: 10.1242/dev.202703
Lakshmy Vasan, Vorapin Chinchalongporn, Fermisk Saleh, Dawn Zinyk, Cao Ke, Hamsini Suresh, Hussein Ghazale, Lauren Belfiore, Yacine Touahri, Ana-Maria Oproescu, Shruti Patel, Matthew Rozak, Yutaka Amemiya, Sisu Han, Alexandra Moffat, Sandra E Black, JoAnne McLaurin, Jamie Near, Arun Seth, Maged Goubran, Orly Reiner, Jesse Gillis, Chao Wang, Satoshi Okawa, Carol Schuurmans
{"title":"Examining the NEUROG2 lineage and associated gene expression in human cortical organoids.","authors":"Lakshmy Vasan, Vorapin Chinchalongporn, Fermisk Saleh, Dawn Zinyk, Cao Ke, Hamsini Suresh, Hussein Ghazale, Lauren Belfiore, Yacine Touahri, Ana-Maria Oproescu, Shruti Patel, Matthew Rozak, Yutaka Amemiya, Sisu Han, Alexandra Moffat, Sandra E Black, JoAnne McLaurin, Jamie Near, Arun Seth, Maged Goubran, Orly Reiner, Jesse Gillis, Chao Wang, Satoshi Okawa, Carol Schuurmans","doi":"10.1242/dev.202703","DOIUrl":"10.1242/dev.202703","url":null,"abstract":"<p><p>Proneural genes are conserved drivers of neurogenesis across the animal kingdom. How their functions have adapted to guide human-specific neurodevelopmental features is poorly understood. Here, we mined transcriptomic data from human fetal cortices and generated from human embryonic stem cell-derived cortical organoids (COs) to show that NEUROG1 and NEUROG2 are most highly expressed in basal neural progenitor cells, with pseudotime trajectory analyses indicating that NEUROG1-derived lineages predominate early and NEUROG2 lineages later. Using ChIP-qPCR, gene silencing and overexpression studies in COs, we show that NEUROG2 is necessary and sufficient to directly transactivate known target genes (NEUROD1, EOMES, RND2). To identify new targets, we engineered NEUROG2-mCherry knock-in human embryonic stem cells for CO generation. The mCherry-high CO cell transcriptome is enriched in extracellular matrix-associated genes, and two genes associated with human-accelerated regions: PPP1R17 and FZD8. We show that NEUROG2 binds COL1A1, COL3A1 and PPP1R17 regulatory elements, and induces their ectopic expression in COs, although NEUROG2 is not required for this expression. Neurog2 similarly induces Col3a1 and Ppp1r17 in murine P19 cells. These data are consistent with a conservation of NEUROG2 function across mammalian species.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827604","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 : 2025-01-15Epub Date: 2025-01-20DOI: 10.1242/dev.204264
Lauren Bobzin, Audrey Nickle, Sebastian Ko, Michaela Ince, Aaron Huang, Arshia Bhojwani, Ryan Roberts, Amy E Merrill
{"title":"FGFR2 directs inhibition of WNT signaling to regulate anterior fontanelle closure during skull development.","authors":"Lauren Bobzin, Audrey Nickle, Sebastian Ko, Michaela Ince, Aaron Huang, Arshia Bhojwani, Ryan Roberts, Amy E Merrill","doi":"10.1242/dev.204264","DOIUrl":"10.1242/dev.204264","url":null,"abstract":"<p><p>The calvarial bones of the infant skull are linked by transient fibrous joints known as sutures and fontanelles, which are essential for skull compression during birth and expansion during postnatal brain growth. Genetic conditions caused by pathogenic variants in FGFR2, such as Apert, Pfeiffer, and Crouzon syndromes, result in calvarial deformities due to premature suture fusion and a persistently open anterior fontanelle (AF). In this study, we investigated how Fgfr2 regulates AF closure by leveraging mouse genetics and single-cell transcriptomics. We find that AF cells, marked by the tendon/ligament factor SCX, are spatially organized into ecto- and endocranial domains that selectively differentiate into ligament, bone, and cartilage to form the posterior frontal suture. We show that AF cell differentiation is non-autonomously regulated by FGFR2 signaling in osteogenic front cells of the frontal bones, which regulate WNT signaling in neighboring AF cells by expressing the secreted WNT inhibitor Wif1. Upon loss of Fgfr2, Wif1 expression is downregulated, and AF cells fail to form the posterior frontal suture. This study identifies an FGF-WNT signaling circuit that that directs suture formation within the AF during postnatal development.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946426","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}