DevelopmentPub Date : 2025-08-15Epub Date: 2025-08-26DOI: 10.1242/dev.204678
Reagan Lamb, Michael Scales, Julie Watkins, Martin Werner, Salvatore J Cherra
{"title":"A PDZ-RapGEF promotes synaptic development in Caenorhabditis elegans through a Rap/Rac signaling pathway.","authors":"Reagan Lamb, Michael Scales, Julie Watkins, Martin Werner, Salvatore J Cherra","doi":"10.1242/dev.204678","DOIUrl":"10.1242/dev.204678","url":null,"abstract":"<p><p>Small G proteins coordinate the development of nerve terminals. The activity of G proteins is finely tuned by GTPase regulatory proteins. Previously, we have observed that PXF-1, a Caenorhabditis elegans GTPase regulatory protein, is required for the function of cholinergic motor neurons. Here, we investigated how PXF-1 coordinates the development of presynaptic terminals at the molecular level. We observed that PXF-1 acts through RAP-1 to promote synapse development. Subsequently, we found that pxf-1 mutants display a reduction in RAC-2 activity, which is required for cholinergic synapse development. We observed that RAC-2 acts downstream of RAP-1. Finally, we identified a physical interaction between RAP-1 and TIAM-1, a Rac guanine exchange factor, which links PXF-1 function to the presynaptic actin cytoskeleton through RAC-2 activation. These findings highlight how small G protein signaling pathways interact to coordinate the development of presynaptic terminals.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759460","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 : 2025-08-15DOI: 10.1242/dev.205094
{"title":"Pathway to Independence - an interview with Max Farnworth.","authors":"","doi":"10.1242/dev.205094","DOIUrl":"10.1242/dev.205094","url":null,"abstract":"<p><p>Max Farnworth completed his PhD in Gregor Bucher's lab at the University of Göttingen, Germany, where he explored how heterochrony shapes the evolution and development of insect brains. He then joined the lab of Stephen Montgomery at the University of Bristol supported by a Walter Benjamin Scholarship, to investigate how two enigmatic brain regions co-evolve to support novel behaviours, using neotropical butterflies as a model system. Currently, Max is a Senior Research Associate developing new tools to study the evolution of neural circuits. Max has been selected as one of our 2025 PI fellows, a group of researchers who will be supported by Development's Pathway to Independence programme as they aim to secure independent positions. We spoke to Max to learn more about why he decided to apply to the programme, and what research questions he hopes to address with his own lab.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 16","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854864","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 : 2025-08-15DOI: 10.1242/dev.204919
Asya Dolgikh, Samuel Rommelaere, Aseel Ghanem, Bianca Petrignani, Mickael Poidevin, Estee Kurant, Bruno Lemaitre
{"title":"The secreted Nimrod protein NimB1 negatively regulates early steps of apoptotic cell phagocytosis in Drosophila.","authors":"Asya Dolgikh, Samuel Rommelaere, Aseel Ghanem, Bianca Petrignani, Mickael Poidevin, Estee Kurant, Bruno Lemaitre","doi":"10.1242/dev.204919","DOIUrl":"10.1242/dev.204919","url":null,"abstract":"<p><p>Efferocytosis, the efficient clearance of apoptotic cells (ACs) by phagocytes, is vital for maintaining tissue homeostasis. Here, we reveal the role of the secreted protein NimB1 in reducing apoptotic cell recognition and binding in the early stages of efferocytosis. NimB1 is expressed in macrophages (also called plasmatocytes) and binds to ACs in a phosphatidylserine-dependent manner. Structural analysis shows that NimB1 shares striking similarities with the bridging molecule NimB4, and possesses two phosphatidylserine-binding motifs, supporting its role in efferocytosis. Larval macrophages of NimB1-null Drosophila mutants display a hyper-phagocytic phenotype characterized by increased engulfment of ACs. Confocal imaging reveals that NimB1 specifically inhibits early steps in internalization of ACs, but does not impact phagosome maturation. We find that NimB1 is a secreted factor that negatively regulates efferocytosis, antagonizing the role of NimB4. Our study and the analogous opposing roles of Draper Isoforms II and I in efferocytosis suggest that a balance of negative and positive regulators allows optimization of the rate of apoptotic cell clearance by macrophages.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658711","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 : 2025-08-15DOI: 10.1242/dev.205053
{"title":"Pathway to Independence - an interview with Toshimichi Yamada.","authors":"","doi":"10.1242/dev.205053","DOIUrl":"10.1242/dev.205053","url":null,"abstract":"<p><p>Toshi Yamada earned his PhD in Chemistry from the University of Tokyo, Japan, where he studied regulatory mechanisms controlling RNA dynamics and stability. He is currently a postdoctoral fellow in Wendell Lim's lab at University of California, San Francisco, working on uncovering the design principles of mammalian embryogenesis and reconstituting developmental processes in vitro. Toshi has been selected as one of our 2025 Pathway to Independence fellows, a group of researchers who will be supported by Development's Pathway to Independence programme as they aim to secure independent positions. We spoke to Toshi to learn more about why he decided to apply to the programme, and what research directions he hopes to pursue with his own lab.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 16","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854866","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 : 2025-08-15Epub Date: 2025-08-26DOI: 10.1242/dev.204508
Zoe Weeks, Gargi Chaturvedi, Emily Day, Steven Kelly, Laura A Moody
{"title":"A FLOE-related protein regulates the two-dimensional to three-dimensional growth transition in the moss Physcomitrium patens.","authors":"Zoe Weeks, Gargi Chaturvedi, Emily Day, Steven Kelly, Laura A Moody","doi":"10.1242/dev.204508","DOIUrl":"10.1242/dev.204508","url":null,"abstract":"<p><p>The colonization of the land by plants coincided with the evolution of three-dimensional (3D) growth: the acquisition of apical cells with the capacity to rotate the plane of cell division. The moss Physcomitrium patens has recently been developed as a model system in which to dissect the genetic basis of 3D growth, a unifying feature of all land plants. The cytokinin-unresponsive nog1-R mutant incorrectly orients division planes in developing buds and thus fails to make the transition to 3D growth. To reveal the genetic interactors of the NOG1 gene, which encodes a protein with a C-terminal UBA domain, we performed a screen and identified the suppressor of nog1a (snog1a) mutant. We have mapped the causative mutation to a gene that encodes a protein related to FLOE2/3 from Arabidopsis and demonstrated that the mutant phenotypes observed in both a nog1 disruptant mutant (nog1dis) and snog1a can be attributed to changes in cytokinin perception. We present a revised model in which NOG1 operates independently of the APB transcription factors to promote 3D growth initiation.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689563","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 : 2025-08-01Epub Date: 2025-08-15DOI: 10.1242/dev.204885
Serge A van de Pavert, Daniela Talarico, Andrea Brendolan
{"title":"Origin and differentiation of lymph node and spleen progenitors during embryonic development.","authors":"Serge A van de Pavert, Daniela Talarico, Andrea Brendolan","doi":"10.1242/dev.204885","DOIUrl":"10.1242/dev.204885","url":null,"abstract":"<p><p>Secondary lymphoid tissues, including the spleen and lymph nodes, play an essential role in supporting immune responses. These organs are structurally organized into specialized compartments in which the interactions between hematopoietic and stromal cells are crucial for immune cell function. In this Review, we examine the cellular and molecular mechanisms that control spleen and lymph nodes, primarily in mice, with a particular emphasis on the embryonic origins of the different cell types involved. We also discuss the processes that determine the acquisition of lymphoid and mesenchymal cell fate in these tissues, as well as the developmental relationships between embryonic progenitor cells and mature stromal cells. In addition, we address the importance of understanding the sources of progenitor cells in the context of organogenesis and highlight several unresolved questions.</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":"144854861","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}
{"title":"EMG1 cooperates with GRHL3 in β-catenin-mediated surface ectoderm differentiation to regulate neural tube closure.","authors":"Chiharu Kimura-Yoshida, Kyoko Mochida, Chihiro Matsuno, Keiko Kano, Emi Mishiro-Sato, Isao Matsuo","doi":"10.1242/dev.204700","DOIUrl":"https://doi.org/10.1242/dev.204700","url":null,"abstract":"<p><p>Grainyhead-like transcription factor 3 (GRHL3) directs surface ectoderm differentiation under the control of the canonical Wnt/β-catenin pathway. However, the molecular mechanisms that control nuclear GRHL3 expression through β-catenin are not fully understood. Here, we show that the essential for mitotic growth 1 (EMG1) protein constitutes a protein complex with GRHL3, and that EMG1 is required for correct nuclear localization of GRHL3, and for activation of the canonical Wnt signaling pathway. Conditional knockout mutation of Emg1 in the GRHL3-positive surface ectoderm causes neural tube defects at the level of the spinal cord, i.e. spina bifida. Additionally, the severity of compound mutant phenotypes of Emg1 and Grhl3 indicates that they interact genetically in neurulation and palate development. These lines of evidence demonstrate that EMG1 cooperates with GRHL3 in β-catenin-mediated surface ectoderm differentiation. Since the EMG1 mutation causes Bowen-Conradi syndrome and the GRHL3 mutation causes Van der Woude syndrome 2, both of which are associated with neural tube dysplasia and cleft palate, our study will help to improve our understanding of the pathogenic mechanisms of these two human genetic diseases.</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":"144783789","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: 2025-08-07DOI: 10.1242/dev.205120
{"title":"The people behind the papers - Chen Pan and Keisuke Shimada.","authors":"","doi":"10.1242/dev.205120","DOIUrl":"10.1242/dev.205120","url":null,"abstract":"<p><p>Pyruvate dehydrogenase E1 subunit alpha 2 (PDHA2) is a testis-specific mitochondrial protein involved in energy metabolism and spermatogenesis. In their study, Keisuke Shimada and colleagues show that PDHA2 is crucial for normal spermatogenesis and it likely compensates for Pdha1, which is normally silenced during meiosis, in male germ cells. To find out more about their work, we spoke to the first author, Chen Pan, and the corresponding author, Keisuke Shimada, Associate Professor at the Laboratory of Disease Models, School of Veterinary Medicine, Rakuno Gakuen University, Japan.</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":"144793723","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: 2025-08-15DOI: 10.1242/dev.204557
Qing Chen, Safia Malki, Xiaojiang Xu, Jiajia Wang, Brian Bennett, Xiaofeng Zheng, Brad L Lackford, Oleksandr Kirsanov, Christopher B Geyer, Guang Hu
{"title":"Cnot3 is required for male germ cell development and spermatogonial stem cell maintenance.","authors":"Qing Chen, Safia Malki, Xiaojiang Xu, Jiajia Wang, Brian Bennett, Xiaofeng Zheng, Brad L Lackford, Oleksandr Kirsanov, Christopher B Geyer, Guang Hu","doi":"10.1242/dev.204557","DOIUrl":"10.1242/dev.204557","url":null,"abstract":"<p><p>The foundation of spermatogenesis and lifelong fertility is provided by spermatogonial stem cells (SSCs). SSCs divide asymmetrically to either self-renew or produce undifferentiated progenitors. However, regulatory mechanisms governing SSC maintenance are poorly understood. Here, we show that the CCR4-NOT mRNA deadenylase complex subunit CNOT3 is essential for sustaining spermatogonial populations in mice. Its deletion in adult germ cells resulted in germ cell loss and infertility, and its deletion in spermatogonia in the developing testis resulted in SSC depletion and compromised spermatogenesis. Consistent with the in vivo results, deletion of Cnot3 in cultured SSCs caused a reduction in cell proliferation and viability, and downregulation of SSC markers. Mechanistically, Cnot3 deletion led to the de-repression of transcripts encoding factors involved in spermatogonial differentiation, including those in the glutathione redox pathway that are crucial for SSC maintenance. Together, our study reveals that CNOT3 - likely via the CCR4-NOT complex - promotes the degradation of transcripts encoding differentiation factors to maintain the SSCs in the stem cell state, highlighting the importance of CCR4-NOT-mediated post-transcriptional gene regulation in SSCs and male germ cell development.</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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12401510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854859","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 : 2025-08-01Epub 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}