DevelopmentPub Date : 2024-09-15Epub Date: 2024-09-20DOI: 10.1242/dev.204379
J Guillermo Sanchez, Scott Rankin, Emily Paul, Heather A McCauley, Daniel O Kechele, Jacob R Enriquez, Nana-Hawa Jones, Siri A W Greeley, Lisa Letourneau-Freiberg, Aaron M Zorn, Mansa Krishnamurthy, James M Wells
{"title":"RFX6 regulates human intestinal patterning and function upstream of PDX1.","authors":"J Guillermo Sanchez, Scott Rankin, Emily Paul, Heather A McCauley, Daniel O Kechele, Jacob R Enriquez, Nana-Hawa Jones, Siri A W Greeley, Lisa Letourneau-Freiberg, Aaron M Zorn, Mansa Krishnamurthy, James M Wells","doi":"10.1242/dev.204379","DOIUrl":"10.1242/dev.204379","url":null,"abstract":"","PeriodicalId":11375,"journal":{"name":"Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11423918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282074","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 non-canonical bivalent gene Wfdc15a controls spermatogenic protease and immune homeostasis.","authors":"Shin-Ichi Tomizawa, Rachel Fellows, Michio Ono, Kazushige Kuroha, Ivana Dočkal, Yuki Kobayashi, Keisuke Minamizawa, Koji Natsume, Kuniko Nakajima, Ikue Hoshi, Shion Matsuda, Masahide Seki, Yutaka Suzuki, Kazushi Aoto, Hirotomo Saitsu, Kazuyuki Ohbo","doi":"10.1242/dev.202834","DOIUrl":"10.1242/dev.202834","url":null,"abstract":"<p><p>Male infertility can be caused by chromosomal abnormalities, mutations and epigenetic defects. Epigenetic modifiers pre-program hundreds of spermatogenic genes in spermatogonial stem cells (SSCs) for expression later in spermatids, but it remains mostly unclear whether and how those genes are involved in fertility. Here, we report that Wfdc15a, a WFDC family protease inhibitor pre-programmed by KMT2B, is essential for spermatogenesis. We found that Wfdc15a is a non-canonical bivalent gene carrying both H3K4me3 and facultative H3K9me3 in SSCs, but is later activated along with the loss of H3K9me3 and acquisition of H3K27ac during meiosis. We show that WFDC15A deficiency causes defective spermiogenesis at the beginning of spermatid elongation. Notably, depletion of WFDC15A causes substantial disturbance of the testicular protease-antiprotease network and leads to an orchitis-like inflammatory response associated with TNFα expression in round spermatids. Together, our results reveal a unique epigenetic program regulating innate immunity crucial for fertility.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105438","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 : 2024-09-15Epub Date: 2024-09-24DOI: 10.1242/dev.202787
Karin C Kiontke, R Antonio Herrera, D Adam Mason, Alyssa Woronik, Stephanie Vernooy, Yash Patel, David H A Fitch
{"title":"Tissue-specific RNA-seq defines genes governing male tail tip morphogenesis in C. elegans.","authors":"Karin C Kiontke, R Antonio Herrera, D Adam Mason, Alyssa Woronik, Stephanie Vernooy, Yash Patel, David H A Fitch","doi":"10.1242/dev.202787","DOIUrl":"10.1242/dev.202787","url":null,"abstract":"<p><p>Caenorhabditis elegans males undergo sex-specific tail tip morphogenesis (TTM) under the control of the DM-domain transcription factor DMD-3. To find genes regulated by DMD-3, we performed RNA-seq of laser-dissected tail tips. We identified 564 genes differentially expressed (DE) in wild-type males versus dmd-3(-) males and hermaphrodites. The transcription profile of dmd-3(-) tail tips is similar to that in hermaphrodites. For validation, we analyzed transcriptional reporters for 49 genes and found male-specific or male-biased expression for 26 genes. Only 11 DE genes overlapped with genes found in a previous RNAi screen for defective TTM. GO enrichment analysis of DE genes finds upregulation of genes within the unfolded protein response pathway and downregulation of genes involved in cuticle maintenance. Of the DE genes, 40 are transcription factors, indicating that the gene network downstream of DMD-3 is complex and potentially modular. We propose modules of genes that act together in TTM and are co-regulated by DMD-3, among them the chondroitin synthesis pathway and the hypertonic stress response.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282057","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 : 2024-09-15Epub Date: 2024-09-24DOI: 10.1242/dev.202943
Jake Turley, Francesca Robertson, Isaac V Chenchiah, Tanniemola B Liverpool, Helen Weavers, Paul Martin
{"title":"Deep learning reveals a damage signalling hierarchy that coordinates different cell behaviours driving wound re-epithelialisation.","authors":"Jake Turley, Francesca Robertson, Isaac V Chenchiah, Tanniemola B Liverpool, Helen Weavers, Paul Martin","doi":"10.1242/dev.202943","DOIUrl":"10.1242/dev.202943","url":null,"abstract":"<p><p>One of the key tissue movements driving closure of a wound is re-epithelialisation. Earlier wound healing studies describe the dynamic cell behaviours that contribute to wound re-epithelialisation, including cell division, cell shape changes and cell migration, as well as the signals that might regulate these cell behaviours. Here, we have used a series of deep learning tools to quantify the contributions of each of these cell behaviours from movies of repairing wounds in the Drosophila pupal wing epithelium. We test how each is altered after knockdown of the conserved wound repair signals Ca2+ and JNK, as well as after ablation of macrophages that supply growth factor signals believed to orchestrate aspects of the repair process. Our genetic perturbation experiments provide quantifiable insights regarding how these wound signals impact cell behaviours. We find that Ca2+ signalling is a master regulator required for all contributing cell behaviours; JNK signalling primarily drives cell shape changes and divisions, whereas signals from macrophages largely regulate cell migration and proliferation. Our studies show deep learning to be a valuable tool for unravelling complex signalling hierarchies underlying tissue repair.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035544","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 : 2024-09-15Epub Date: 2024-09-30DOI: 10.1242/dev.202764
Quentin Lo Giudice, Robin J Wagener, Philipp Abe, Laura Frangeul, Denis Jabaudon
{"title":"Developmental emergence of first- and higher-order thalamic neuron molecular identities.","authors":"Quentin Lo Giudice, Robin J Wagener, Philipp Abe, Laura Frangeul, Denis Jabaudon","doi":"10.1242/dev.202764","DOIUrl":"10.1242/dev.202764","url":null,"abstract":"<p><p>The thalamus is organized into nuclei that have distinct input and output connectivities with the cortex. Whereas first-order (FO) nuclei - also called core nuclei - relay input from sensory organs on the body surface and project to primary cortical sensory areas, higher-order (HO) nuclei - matrix nuclei - instead receive their driver input from the cortex and project to secondary and associative areas within cortico-thalamo-cortical loops. Input-dependent processes have been shown to play a crucial role in the emergence of FO thalamic neuron identity from a ground-state HO neuron identity, yet how this identity emerges during development remains unknown. Here, using single-cell RNA sequencing of the developing mouse embryonic thalamus, we show that, although they are born together, HO neurons start differentiating earlier than FO neurons. Within the FO visual thalamus, postnatal peripheral input is crucial for the maturation of excitatory, but not inhibitory, neurons. Our findings reveal different differentiation tempos and input sensitivities of HO and FO neurons, and highlight neuron type-specific molecular differentiation programs in the developing thalamus.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343729","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 : 2024-09-15Epub Date: 2024-09-16DOI: 10.1242/dev.204337
{"title":"Transitions in development - an interview with Margarete Diaz Cuadros.","authors":"","doi":"10.1242/dev.204337","DOIUrl":"https://doi.org/10.1242/dev.204337","url":null,"abstract":"<p><p>Margarete is a Junior Fellow in the Department of Molecular Biology at Massachusetts General Hospital (MGH) in Boston, USA. Margarete's group (www.diazcuadroslab.org) seeks to reveal the molecular, metabolic and genetic regulation of developmental timing in animals using in vivo and in vitro approaches. We spoke to Margarete over Teams to learn more about her transition to becoming a group leader, her philosophy for creating a positive lab environment and the importance of removing barriers for under-represented communities in science.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282075","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 : 2024-09-15Epub Date: 2024-09-30DOI: 10.1242/dev.202303
Balint Der, Helena Bugacov, Bohdana-Myroslava Briantseva, Andrew P McMahon
{"title":"Cadherin adhesion complexes direct cell aggregation in the epithelial transition of Wnt-induced nephron progenitor cells.","authors":"Balint Der, Helena Bugacov, Bohdana-Myroslava Briantseva, Andrew P McMahon","doi":"10.1242/dev.202303","DOIUrl":"10.1242/dev.202303","url":null,"abstract":"<p><p>In the developing mammalian kidney, nephron formation is initiated by a subset of nephron progenitor cells (NPCs). Wnt input activates a β-catenin (Ctnnb1)-driven, transcriptional nephrogenic program and the mesenchymal to epithelial transition (MET) of NPCs. Using an in vitro mouse NPC culture model, we observed that activation of the Wnt pathway results in the aggregation of induced NPCs, which is an initiating step in the MET program. Genetic removal showed aggregation was dependent on β-catenin. Modulating extracellular Ca2+ levels showed cell-cell contacts were Ca2+ dependent, suggesting a role for cadherin (Cdh)-directed cell adhesion. Molecular analysis identified Cdh2, Cdh4 and Cdh11 in NPCs, and the β-catenin directed upregulation of Cdh3 and Cdh4 accompanying the MET of induced NPCs. Mutational analysis of β-catenin supported a role for a Lef/Tcf-β-catenin-mediated transcriptional response in the cell aggregation process. Genetic removal of all four cadherins, and independent removal of α-catenin or of β-catenin-α-catenin interactions, abolished aggregation, but not the inductive response to Wnt pathway activation. These findings, and data in an accompanying article highlight the role of β-catenin in linking transcriptional programs to the morphogenesis of NPCs in mammalian nephrogenesis.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343728","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 : 2024-09-15Epub Date: 2024-09-26DOI: 10.1242/dev.204385
{"title":"The people behind the papers - Yasmine el Azhar and Ina Sonnen.","authors":"","doi":"10.1242/dev.204385","DOIUrl":"https://doi.org/10.1242/dev.204385","url":null,"abstract":"<p><p>Hes proteins are transcription factors that are dynamically expressed during embryonic development, but it remains unclear how the oscillations in Hes expression differ across cell types during development. In this new study, Ina Sonnen and colleagues find that the Notch-driven Hes1 oscillation dynamics in the mouse embryonic tail are cell-type specific. To find out more about the story behind the paper, we caught up with first author Yasmine el Azhar and corresponding author Ina Sonnen, Group Leader at the Hubrecht Institute, The Netherlands.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343730","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 : 2024-09-15Epub Date: 2024-09-24DOI: 10.1242/dev.204372
{"title":"The people behind the papers - Jake Turley.","authors":"","doi":"10.1242/dev.204372","DOIUrl":"10.1242/dev.204372","url":null,"abstract":"<p><p>During wound healing, epithelial cells divide, migrate and change shape. However, it is unclear how much these different cell behaviours contribute to the closure of the wound. A new paper in Development applies deep learning models to analyse large imaging datasets from the Drosophila pupa and quantify the contributions of the different cell behaviours. To learn more about the story behind the paper, we caught up with first author Jake Turley. Jake was a PhD student in Bristol, UK, but is now a Research Fellow at the Mechanobiology Institute, National University of Singapore.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307315","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 : 2024-09-15Epub Date: 2024-09-17DOI: 10.1242/dev.203080
Kenta Niimi, Jun Nakae, Yoshiaki Kubota, Shinobu Inagaki, Tatsuo Furuyama
{"title":"Macrophages play a crucial role in vascular smooth muscle cell coverage.","authors":"Kenta Niimi, Jun Nakae, Yoshiaki Kubota, Shinobu Inagaki, Tatsuo Furuyama","doi":"10.1242/dev.203080","DOIUrl":"10.1242/dev.203080","url":null,"abstract":"<p><p>The microvascular system consists of two cell types: endothelial and mural (pericytes and vascular smooth muscle cells; VSMCs) cells. Communication between endothelial and mural cells plays a pivotal role in the maintenance of vascular homeostasis; however, in vivo molecular and cellular mechanisms underlying mural cell development remain unclear. In this study, we found that macrophages played a crucial role in TGFβ-dependent pericyte-to-VSMC differentiation during retinal vasculature development. In mice with constitutively active Foxo1 overexpression, substantial accumulation of TGFβ1-producing macrophages and pericytes around the angiogenic front region was observed. Additionally, the TGFβ-SMAD pathway was activated in pericytes adjacent to macrophages, resulting in excess ectopic α-smooth muscle actin-positive VSMCs. Furthermore, we identified endothelial SEMA3C as an attractant for macrophages. In vivo neutralization of SEMA3C rescued macrophage accumulation and ectopic VSMC phenotypes in the mice, as well as drug-induced macrophage depletion. Therefore, macrophages play an important physiological role in VSMC development via the FOXO1-SEMA3C pathway.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016666","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}