Development最新文献_第3页

Chd4 remodels chromatin to control retinal cell type specification and lineage termination. Chd4重塑染色质，控制视网膜细胞类型规范和谱系终止。

IF 3.6 2区生物学

Development Pub Date : 2025-10-15 Epub Date: 2025-09-18 DOI: 10.1242/dev.204697

Sujay Shah, Suma Medisetti, José Alex Lourenço Fernandes, Pierre Mattar

{"title":"Chd4 remodels chromatin to control retinal cell type specification and lineage termination.","authors":"Sujay Shah, Suma Medisetti, José Alex Lourenço Fernandes, Pierre Mattar","doi":"10.1242/dev.204697","DOIUrl":"10.1242/dev.204697","url":null,"abstract":"During development, neural progenitor cells modify their output over time to produce different types of neurons and glia in chronological sequences. Epigenetic processes have been shown to regulate neural progenitor potential, but the underlying mechanisms are not well understood. Here, we generated retina-specific conditional mouse knockouts (cKOs) in the key nucleosome remodeller Chd4. Chd4 cKOs overproduced early-born retinal ganglion and amacrine cells. Postnatally, later-born rod photoreceptors were drastically underproduced. Progenitors failed to differentiate into Müller glia on schedule and continued to proliferate beyond their normal developmental window. Next, to determine how Chd4 regulates the genome, we performed CUT&RUN-seq and ATAC-seq, revealing that genome accessibility was significantly increased at ∼10,000 regulatory elements. Accordingly, multiplexed single-cell transcriptomics demonstrated that deletion of Chd4 led to corresponding increases in transcription. These results suggest that Chd4 restricts the genome to repress progenitor identity and promote differentiation. Taken together, our data suggest that Chd4-dependent nucleosome remodelling plays a crucial role in the temporal transition that governs lineage termination, but does not regulate earlier temporal transitions.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12517350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991702","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}

引用次数: 0

Planarian microtubules form a network within muscle and regulate injury-induced genes essential for regeneration patterning. 涡虫微管在肌肉内形成一个网络，并调节再生模式所必需的损伤诱导基因。

IF 3.6 2区生物学

Development Pub Date : 2025-10-15 Epub Date: 2025-10-16 DOI: 10.1242/dev.204669

Xavier N Anderson, Christian P Petersen

{"title":"Planarian microtubules form a network within muscle and regulate injury-induced genes essential for regeneration patterning.","authors":"Xavier N Anderson, Christian P Petersen","doi":"10.1242/dev.204669","DOIUrl":"https://doi.org/10.1242/dev.204669","url":null,"abstract":"Planarian muscle produces key wound signal patterning whole-body regeneration. Within muscle, generic induction of wnt1 promotes tail regeneration, while polarized expression of the Wnt inhibitor notum at anterior-facing wounds drives head regeneration. Classic experiments indicate that microtubules are also involved in blastema fating, but the cell biology of planarian muscle is still poorly understood. We raised an antibody to muscle-expressed TUBA-2 and found that planarian muscle possesses a microtubule network linking contractile fibers with their mononucleated cell bodies. Microtubules were required for muscle fiber regrowth across wound sites at times that correlated with expression of wound-induced genes. Expression profiling found that sublethal colchicine treatment disrupted a subset of muscle-expressed injury-induced genes, with strongest effects on wnt1 and notum. Higher colchicine doses (>200 µg/ml) prevented wnt1 and notum expression, while, surprisingly, lower doses (125 µg/ml) elevated notum at posterior-facing wounds, thereby implicating microtubules in both the activation and polarization of genes expressed from injured muscle. Furthermore, microtubules functionally interact with Wnts to control head/tail determination. Together, planarian microtubules act in specific regulatory pathways to express key muscle-expressed and injury-induced factors used for blastema fating.","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":"145299210","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}

引用次数: 0

Wnt signalling maintains self-renewal of human hepatoblasts without blocking their differentiation. Wnt信号传导维持人肝母细胞的自我更新而不阻断其分化。

IF 3.6 2区生物学

Development Pub Date : 2025-10-10 DOI: 10.1242/dev.205026

Ekaterini D Zacharis, Carola M Morell, Rute A Tomaz, Arash Shahsavari, Charlotte Grey-Wilson, Maïa Pesic, Vasileios Galanakis, Eleanor C Williams, Irina Mohorianu, Irene Talon, Ludovic Vallier

{"title":"Wnt signalling maintains self-renewal of human hepatoblasts without blocking their differentiation.","authors":"Ekaterini D Zacharis, Carola M Morell, Rute A Tomaz, Arash Shahsavari, Charlotte Grey-Wilson, Maïa Pesic, Vasileios Galanakis, Eleanor C Williams, Irina Mohorianu, Irene Talon, Ludovic Vallier","doi":"10.1242/dev.205026","DOIUrl":"https://doi.org/10.1242/dev.205026","url":null,"abstract":"Hepatoblasts play a key role in liver organogenesis by differentiating into hepatocytes and cholangiocytes, the main functional cell types of the liver. Mouse studies have shown the association of Wnt signalling with proliferation and differentiation of hepatoblasts. However, the exact function of this pathway in hepatic development is not fully uncovered, especially in human. Here, we use hepatoblast organoids (HBOs) derived from human foetal livers to investigate the importance of Wnt signalling in self-renewal and cell fate decisions during liver development. We first showed that Wnt plays a key role in hepatoblast self-renewal capacity in vitro by maintaining their proliferative state. However, Wnt was not sufficient to block differentiation of HBOs into hepatocytes or cholangiocytes, suggesting that other factors are necessary to maintain hepatoblast bipotency. Finally, single-cell transcriptomic analyses revealed that Wnt signalling activity correlates with hepatoblast proliferation in the human foetal liver, suggesting that the role for Wnt could be conserved in vivo. Taken together, our results support a model where Wnt signalling acts to preserve the proliferative capacity of hepatoblasts without being sufficient to maintain their bipotent state.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274004","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}

引用次数: 0

A molecular, spatial, and regulatory atlas of the Hydra vulgaris nervous system. 水螅神经系统的分子、空间和调控图谱。

IF 3.6 2区生物学

Development Pub Date : 2025-10-10 DOI: 10.1242/dev.204983

Hannah Morris Little, Abby S Primack, Jennifer Tsverov, Michael P Nunneley, Susanne Mühlbauer, Ben D Cox, Christina Busse, Sandra Schneid, Amber Louwagie, Jack F Cazet, Charles N David, Jeffrey A Farrell, Celina E Juliano

{"title":"A molecular, spatial, and regulatory atlas of the Hydra vulgaris nervous system.","authors":"Hannah Morris Little, Abby S Primack, Jennifer Tsverov, Michael P Nunneley, Susanne Mühlbauer, Ben D Cox, Christina Busse, Sandra Schneid, Amber Louwagie, Jack F Cazet, Charles N David, Jeffrey A Farrell, Celina E Juliano","doi":"10.1242/dev.204983","DOIUrl":"10.1242/dev.204983","url":null,"abstract":"Hydra vulgaris, a cnidarian with a simple nerve net, is an emerging model for developmental, regenerative, and functional neuroscience. Its genetic tractability and capacity for whole-system imaging make it well suited for studying neuron replacement, regeneration, and neural circuit function. Here, we present the most comprehensive molecular and spatial characterization of the H. vulgaris nervous system to date. Using single-cell RNA sequencing, we identified eight neuron types, each defined by distinct neuropeptide expression, and further resolved these into fifteen transcriptionally distinct subtypes with unique spatial distributions and morphologies. These data enabled a detailed examination of the molecular components of neuronal communication and excitability. To investigate the gene regulatory networks underlying neuronal differentiation, we applied trajectory inference, identified key transcription factors, and performed ATAC-seq on sorted neurons to map chromatin accessibility. All datasets are available through an interactive, user-friendly web portal to support broad use by the research community. Together, these resources provide a foundation for uncovering molecular mechanisms that govern nervous system development, homeostasis, regeneration, and function in H. vulgaris.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273911","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}

引用次数: 0

The ratio of Wnt signaling activity to Sox2 transcription factor levels predicts neuromesodermal fate potential. Wnt信号活性与Sox2转录因子水平的比值可预测神经中胚层命运潜能。

IF 3.6 2区生物学

Development Pub Date : 2025-10-10 DOI: 10.1242/dev.204661

Robert M Morabito, David Tatarakis, Ryan Swick, Samantha Stettnisch, Pavan K Nayak, Thomas F Schilling, Julia A Horsfield, Benjamin L Martin

{"title":"The ratio of Wnt signaling activity to Sox2 transcription factor levels predicts neuromesodermal fate potential.","authors":"Robert M Morabito, David Tatarakis, Ryan Swick, Samantha Stettnisch, Pavan K Nayak, Thomas F Schilling, Julia A Horsfield, Benjamin L Martin","doi":"10.1242/dev.204661","DOIUrl":"10.1242/dev.204661","url":null,"abstract":"Neuromesodermal progenitors (NMPs) are a vertebrate cell type that contribute descendants to both the spinal cord and the mesoderm. The undifferentiated bipotential NMP state is maintained when both Wnt signaling is active and Sox2 is present. We used transgenic reporter lines to live-image both Wnt activity and Sox2 levels in NMPs and observed a unique cellular ratio in NMPs compared to NMP-derived mesoderm or neural tissue. We used this unique signature to identify the previously unknown anatomical position of a progenitor population that gives rise to midline tissues of the floor plate of the spinal cord and the mesodermal notochord. Thus, quantification of the active Wnt signaling to Sox2 ratio can be used to predict and identify cells with neuromesodermal potential. We also developed the auxin inducible 2 degron system for use in zebrafish to test the temporal role that Sox2 plays during midline formation. We found ectopic Sox2 in the presence of Wnt activity holds cells in the undifferentiated floor plate/notochord progenitor state, and that degradation of the ectopic Sox2 is required for cells to adopt a notochord fate.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274094","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}

引用次数: 0

Hemilineage-specific deployment of the pro-apoptotic RHG genes reaper and grim during neurogenesis sculpts segment and sex-specific neural network composition in Drosophila. 促凋亡RHG基因reaper和grim在果蝇神经发生雕刻段和性别特异性神经网络组成中的半谱系特异性部署。

IF 3.6 2区生物学

Development Pub Date : 2025-10-09 DOI: 10.1242/dev.204902

Connor J Sproston, Julia E Rak, Elizabeth C Marin, Shu Kondo, Darren W Williams

{"title":"Hemilineage-specific deployment of the pro-apoptotic RHG genes reaper and grim during neurogenesis sculpts segment and sex-specific neural network composition in Drosophila.","authors":"Connor J Sproston, Julia E Rak, Elizabeth C Marin, Shu Kondo, Darren W Williams","doi":"10.1242/dev.204902","DOIUrl":"https://doi.org/10.1242/dev.204902","url":null,"abstract":"During development populations of neuronal stem cells generate neurons in a modular fashion to produce a striking diversity of subtypes. Within the Drosophila central nervous system a stereotyped, segmentally repeated array of stem cells, called neuroblasts, generate identifiable lineages of neurons, each comprised of 2 hemilineages. Here we show that a key part of early fate determination within a hemilineage is selective neuronal cell death. This precise deletion of neurons occurs throughout the nervous system removing neurons of every transmitter type in a segment-specific fashion. Using Hybridisation Chain Reaction in-situ (HCR) we reveal the proapoptotic RHG genes reaper and grim, but not hid, are transcribed within doomed neurons. Novel T2A-GAL4 knock-in reporters for reaper and grim reveal complex but repeatable expression patterns within hemilineages. These data support functional analysis with null mutants showing that reaper and grim play a complex role in sculpting lineage populations We show that segmental and sex-specific differences in neuronal subtypes is mediated by a temporal switching to death within identified hemilineages during neurogenesis to shape adult networks.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250326","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}

引用次数: 0

Gli FHV mice: a novel tool to investigate GLI processing and localization. Gli FHV小鼠：研究Gli加工和定位的新工具。

IF 3.6 2区生物学

Development Pub Date : 2025-10-08 DOI: 10.1242/dev.204251

Hannah Schrader Dear, Nicole E Franks, Ella E Markley, Alexander M Holtz, Jane Y Song, Craig N Johnson, Paola I Medina-Cabrera, Daniela Hernandez, Praise Joel, Marina Pasca di Magliano, Deneen M Wellik, Benjamin L Allen

{"title":"Gli FHV mice: a novel tool to investigate GLI processing and localization.","authors":"Hannah Schrader Dear, Nicole E Franks, Ella E Markley, Alexander M Holtz, Jane Y Song, Craig N Johnson, Paola I Medina-Cabrera, Daniela Hernandez, Praise Joel, Marina Pasca di Magliano, Deneen M Wellik, Benjamin L Allen","doi":"10.1242/dev.204251","DOIUrl":"https://doi.org/10.1242/dev.204251","url":null,"abstract":"GLI proteins (GLI1-3) are the transcriptional effectors of mammalian Hedgehog (HH) signaling. However, studies of GLI function have been hampered by the lack of robust GLI antibodies. To address this, we utilized CRISPR-based gene editing to generate endogenous epitope-tagged Gli alleles for each Gli gene (Gli1FLAG, Gli2HA, Gli3V5). Through breeding, we established a novel mouse model, Gli1FLAG/FLAG;Gli2HA/HA;Gli3V5/V5, referred to as GliFHV. Importantly, GliFHV animals are viable and fertile with no overt phenotypes. Sanger and long-range DNA sequencing confirmed proper editing of each Gli allele, while qPCR and western blot analysis confirmed similar gene expression and protein levels, respectively, between wildtype and GliFHV animals. We utilized these mice to assess GLI localization in the developing limb, finding that all three GLIs localize to primary cilia with distinct distributions. Finally, we generated immortalized GliFHV mouse embryonic fibroblasts (MEFs), demonstrating that these cells are HH-responsive and that GLIs localize to primary cilia and nuclei in a HH-dependent fashion. These animals and cell lines provide a valuable resource for analyses of GLI processing, localization and function throughout embryogenesis, postnatal development, and in adults.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244218","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}

引用次数: 0

DNAH10 interacts with UCHL3-PACRG complex to coordinate sperm head and flagella development during spermiogenesis. 在精子发生过程中，DNAH10与UCHL3-PACRG复合物相互作用，协调精子头和鞭毛的发育。

IF 3.6 2区生物学

Development Pub Date : 2025-10-08 DOI: 10.1242/dev.204906

Rui Zheng, Jierui Yan, Yuting Wen, Yazhen Wei, Weiwei Zhi, Chaofeng Tu, Yueqiu Tan, Wenming Xu

{"title":"DNAH10 interacts with UCHL3-PACRG complex to coordinate sperm head and flagella development during spermiogenesis.","authors":"Rui Zheng, Jierui Yan, Yuting Wen, Yazhen Wei, Weiwei Zhi, Chaofeng Tu, Yueqiu Tan, Wenming Xu","doi":"10.1242/dev.204906","DOIUrl":"https://doi.org/10.1242/dev.204906","url":null,"abstract":"Asthenoteratozoospermia is a common underlying cause of male infertility, with dynein dysfunction playing an important role in the aetiology of the condition. Dysfunction in certain dynein proteins has been implicated in asthenoteratozoospermia, while others exclusively induce asthenozoospermia in the absence of overt morphological abnormalities in the sperm. Dynein axonemal heavy chain 10 (DNAH10), an inner dynein arm heavy chain protein, was identified as being associated with asthenoteratozoospermia in our previous studies. However, the mechanism through which DNAH10 contributes to this condition remains unclear. In this study, we demonstrated that DNAH10 deficiency leads to abnormal morphology of the sperm head and flagella. Additionally, DNAH10 dysfunction leads to impaired manchette function and aberrant localisation of axonemal proteins. Mechanistically, ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) binds to Parkin co-regulated gene protein (PACRG) and stabilises it via deubiquitination. In this process, DNAH10 exerts a bridging effect, enhancing the interaction between the UCHL3-PACRG complex to facilitate their involvement in manchette function. Collectively, this study demonstrated the function of DNAH10 in intra-manchette transport, providing important guidance for genetic diagnosis and prognosis in patients with infertility.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244204","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}

引用次数: 0

Signals from the head and germinative region differentially regulate regeneration competence of the tapeworm Hymenolepis diminuta. 来自头部和萌发区的信号对小膜绦虫再生能力的调控存在差异。

IF 3.6 2区生物学

Development Pub Date : 2025-10-07 DOI: 10.1242/dev.204781

Elise McCollough Nanista, Landon Elizabeth Poythress, Isabell Reese Skipper, Trevor Haskins, Marieher Felix Cora, Tania Rozario

{"title":"Signals from the head and germinative region differentially regulate regeneration competence of the tapeworm Hymenolepis diminuta.","authors":"Elise McCollough Nanista, Landon Elizabeth Poythress, Isabell Reese Skipper, Trevor Haskins, Marieher Felix Cora, Tania Rozario","doi":"10.1242/dev.204781","DOIUrl":"10.1242/dev.204781","url":null,"abstract":"Competence to regenerate lost tissues varies widely across species. The rat tapeworm, Hymenolepis diminuta, undergoes continual cycles of shedding and regenerating thousands of reproductive segments to propagate the species. Despite its prowess, H. diminuta can only regenerate posteriorly from a singular tissue: the neck or germinative region (GR). What cells and signaling pathways restrict regeneration competence to the GR? In this study, we show that the head regulates regeneration competence by promoting maintenance of the GR and inhibiting proglottid formation in a distance-dependent manner. Anterior-posterior (A-P) patterning within the GR provide local signals that contribute to these responses. βcat1 is necessary for stem cell maintenance, proliferation and proglottidization. On the other hand, sfrp is necessary for maintaining the GR at its proper length. Our study demonstrates that the head organizes a balance of pro- and anti-regeneration signals that must be integrated together and therefore control competence to regenerate.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238214","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}

引用次数: 0

Antagonism between JAK/STAT downstream targets controls stem cell proliferation, cell fate conversion and tumorigenesis. JAK/STAT下游靶点之间的拮抗作用控制着干细胞增殖、细胞命运转化和肿瘤发生。

IF 3.6 2区生物学

Development Pub Date : 2025-10-06 DOI: 10.1242/dev.204701

Hanfei Zhao, Min Wei, Ruiyan Kong, Zhengran Li, Juan Li, Xihui Yang, Jing Wei, Xieyue Liu Tao, Danjie Zhang, Hang Zhao, Yankun Ma, Ningfang Li, Yudan Wang, Lin Shi, Meifang Ma, Jinjun Wang, Ran Xu, Min Zhang, Yongqiang Wang, Zhouhua Li

{"title":"Antagonism between JAK/STAT downstream targets controls stem cell proliferation, cell fate conversion and tumorigenesis.","authors":"Hanfei Zhao, Min Wei, Ruiyan Kong, Zhengran Li, Juan Li, Xihui Yang, Jing Wei, Xieyue Liu Tao, Danjie Zhang, Hang Zhao, Yankun Ma, Ningfang Li, Yudan Wang, Lin Shi, Meifang Ma, Jinjun Wang, Ran Xu, Min Zhang, Yongqiang Wang, Zhouhua Li","doi":"10.1242/dev.204701","DOIUrl":"https://doi.org/10.1242/dev.204701","url":null,"abstract":"Proper proliferation and differentiation of adult stem cells maintains tissue homeostasis. However, how cell proliferation and fate conversion are regulated by niche signals remains poorly understood. Here, we systemically identify JAK/STAT downstream targets in adult Drosophila testis using multi-omics approaches. ubr5, encoding an HECT type E3 ligase, is identified as a putative JAK/STAT target. Depletion of ubr5 in somatic cyst cells affects the proliferation and differentiation of cyst stem cell (CySC) and germline stem cell (GSC). Importantly, ubr5-defective CySC-like cells adopt hub cell fate. Mechanistically, UBR5 interacts with Drumstick (Drm), another putative JAK/STAT target, through its UBR domain and mediates Drm poly-ubiquitination for proteolysis. Ectopic expression of drm mimics ubr5-depleted testes and further removal of drm significantly suppresses the defects observed in ubr5-depleted testes. Finally, the function of UBR5 in stem cell regulation is evolutionarily conserved. Collectively, antagonism between JAK/STAT targets controls JAK/STAT signaling duration, stem cell proliferation/differentiation, and cell fate conversion within the testicular niche. Thus our study uncovers the underlying mechanism of how stem cell proliferation and fate conversion are properly controlled during tissue homeostasis and tumorigenesis.","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231751","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}

引用次数: 0