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Opposing roles for lipocalins and a CD36 family scavenger receptor in apical extracellular matrix-dependent protection of narrow tube integrity. 脂质钙素和CD36家族清道夫受体在细胞外基质依赖的尖管完整性保护中的相反作用。
IF 3.6 2区 生物学
Development Pub Date : 2026-08-15 Epub Date: 2026-01-12 DOI: 10.1242/dev.205309
Alexandra C Belfi, Sage G Aviles, Rachel Forman-Rubinsky, Hasreet K Gill, Jennifer D Cohen, Aleksandra Nawrocka, Axelle Bourez, Pierre van Antwerpen, Patrick Laurent, Meera V Sundaram
{"title":"Opposing roles for lipocalins and a CD36 family scavenger receptor in apical extracellular matrix-dependent protection of narrow tube integrity.","authors":"Alexandra C Belfi, Sage G Aviles, Rachel Forman-Rubinsky, Hasreet K Gill, Jennifer D Cohen, Aleksandra Nawrocka, Axelle Bourez, Pierre van Antwerpen, Patrick Laurent, Meera V Sundaram","doi":"10.1242/dev.205309","DOIUrl":"10.1242/dev.205309","url":null,"abstract":"<p><p>All exposed epithelial surfaces, including the walls of internal tubes, are lined by a lipid and glycoprotein-rich apical extracellular matrix (aECM) that helps shape and protect the apical domain. Secreted lipocalins are lipid transporters frequently found within apical compartments. We show that loss of the Caenorhabditis elegans lipocalin LPR-1 disrupts the assembly of another lipocalin, LPR-3, within the pre-cuticle aECM that protects and shapes the narrow excretory duct and pore tubes. Loss of SCAV-2, a CD36 family scavenger receptor, restored LPR-3 matrix localization and suppressed the tube shaping defects of lpr-1 and a subset of pre-cuticle mutants, but not lpr-3 mutants. SCAV-2 accumulates at duct and pore apical surfaces and functions locally within these tubes. These data demonstrate that LPR-1 and SCAV-2 have opposing effects on narrow tube integrity by altering the content and organization of the luminal aECM of the tube, possibly by acting as transporters of LPR-3 or an LPR-3 cofactor. These results have broadly relevant implications regarding the importance of lipocalins and scavenger receptors for aECM organization and integrity of the narrowest tubes in the body.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12848578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603252","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
Cell-autonomous control coupled with tissue context regulates the cessation of migration at the site of organ development. 细胞自主控制与组织环境相结合,调节器官发育部位迁移的停止。
IF 3.6 2区 生物学
Development Pub Date : 2026-08-15 Epub Date: 2026-02-20 DOI: 10.1242/dev.205271
Katsiaryna Tarbashevich, Zahra Labbaf, Moritz Ophaus, Jan Schick, Lucas Kühl, Sargon Gross-Thebing, Michal Reichman-Fried, Dennis Hoffmann, Martin Stehling, Jochen Seggewiss, Christian Ruckert, Johanna B Kroll, Jan Philipp Junker, Erez Raz
{"title":"Cell-autonomous control coupled with tissue context regulates the cessation of migration at the site of organ development.","authors":"Katsiaryna Tarbashevich, Zahra Labbaf, Moritz Ophaus, Jan Schick, Lucas Kühl, Sargon Gross-Thebing, Michal Reichman-Fried, Dennis Hoffmann, Martin Stehling, Jochen Seggewiss, Christian Ruckert, Johanna B Kroll, Jan Philipp Junker, Erez Raz","doi":"10.1242/dev.205271","DOIUrl":"10.1242/dev.205271","url":null,"abstract":"<p><p>Organ development relies on interactions among different cell types that form three-dimensional structures to carry out specific tasks. This process often involves active migration of progenitor cells toward specific positions within the embryo, where the cells then become immotile and form stable connections among themselves and with neighboring cells. In this work, we study the process of motility loss using zebrafish primordial germ cells (PGC) as an in vivo model. We show that changes in embryonic tissues as well as cell-autonomous events regulate the behavior of germ cells as they arrive at their target region. Importantly, we find that reduction in germ cell motility is correlated with the decay of RNA encoding for Dead end 1 (Dnd1), a conserved vertebrate RNA-binding protein that is essential for PGC migration. Indeed, decreasing or increasing the level of Dnd1 results in a premature or delayed stop to motility, respectively. These findings represent an RNA decay-based mechanism for timing the duration of cell migration in vivo.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046209","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
Regulation of endothelial cell chromatin availability and transcription factor activity during arterial-venous specification. 动脉-静脉规范过程中内皮细胞染色质可用性和转录因子活性的调节。
IF 3.6 2区 生物学
Development Pub Date : 2026-05-07 DOI: 10.1242/dev.205530
Nicholas W Chavkin, Elizabeth A Nelson, Grace Bradecamp, Jordon Aragon, Lay Teng Ang, Kyle M Loh, Karen K Hirschi
{"title":"Regulation of endothelial cell chromatin availability and transcription factor activity during arterial-venous specification.","authors":"Nicholas W Chavkin, Elizabeth A Nelson, Grace Bradecamp, Jordon Aragon, Lay Teng Ang, Kyle M Loh, Karen K Hirschi","doi":"10.1242/dev.205530","DOIUrl":"https://doi.org/10.1242/dev.205530","url":null,"abstract":"<p><p>Arterial-venous specification of endothelial cells during vascular development requires coordination between intracellular signaling, cell cycle state, and transcription factor activity. However, the intrinsic regulatory mechanisms that govern these processes are poorly understood. To investigate this, we assessed endothelial chromatin accessibility during vascular development. Murine postnatal day (P)6 and P15 retinal endothelial cells were analyzed by single cell Assay for Transposase Accessible Chromatin sequencing, revealing heterogeneous chromatin accessibility across an arterial-venous continuum and in distinct cell cycle states. Enhancer regulatory network analysis predicted transcription factors with differential cell cycle and arterial-venous activity, and many with dual activator and repressor functions, including SOX17. We then validated SOX17 function in human endothelial cells, identifying that it inhibits proliferation and promotes arterial gene expression. Our findings suggest that dual roles of key endothelial transcription factors are regulated by chromatin accessibility in a cell cycle- and subtype-specific manner to control arterial-venous specification.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835151","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
Onset of embryonic and placental defects coincide in 19 of 22 novel mid-gestation lethal murine knockout lines. 22个新的妊娠中期致死性小鼠基因敲除系中有19个出现胚胎和胎盘缺陷。
IF 3.6 2区 生物学
Development Pub Date : 2026-05-07 DOI: 10.1242/dev.205276
Taylor M Guertin, Chip Sisson, Rossella Gargiulo, Olivia Macrorie, Emily L Pease, Hannah E Garth, Joris Vriens, Katrien De Clercq, Jesse Mager, Kimberly D Tremblay
{"title":"Onset of embryonic and placental defects coincide in 19 of 22 novel mid-gestation lethal murine knockout lines.","authors":"Taylor M Guertin, Chip Sisson, Rossella Gargiulo, Olivia Macrorie, Emily L Pease, Hannah E Garth, Joris Vriens, Katrien De Clercq, Jesse Mager, Kimberly D Tremblay","doi":"10.1242/dev.205276","DOIUrl":"https://doi.org/10.1242/dev.205276","url":null,"abstract":"<p><p>The focus on assessing embryo-specific defects in lethal knockout (KO) mouse lines has resulted in an underrepresentation of documented placental abnormalities. Presented herein is a uniform analysis of 22 distinct KO mouse lines that exhibit homozygous lethality in a narrow mid-gestation window. All genes altered by each KO have human orthologs, most are implicated in human disease, yet almost all are understudied. To unravel the role each plays in mammalian development, null embryonic and placental phenotype analysis was performed, and wild type (WT) expression of each KO gene was assessed. While the null phenotype of each KO line falls into two broad embryonic categories, the placental phenotypes are diverse and coincide with the onset of gross embryonic defects. The co-occurrence of null embryonic and placental defect onset coupled with WT gene expression highlights that many could be essential in either the embryo or placenta. This analysis serves to guide mid-gestation placental analysis, underscores the importance of routine analysis of the entire conceptus during mid-gestation lethality, and provides functional annotation for each understudied human ortholog.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835214","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
DNAI4 is required for flagellum assembly and male fertility in mice. DNAI4是小鼠鞭毛组装和雄性生殖所必需的。
IF 3.6 2区 生物学
Development Pub Date : 2026-05-05 DOI: 10.1242/dev.205190
Fan Yang, Shiqi Meng, Wenting Lu, Jiayi Su, Guanghua Li, Tingting Ge, Yichun Zhao, Eoin C Whelan, Lu Yuan, Yueqi Yang, Fengming Zhang, Xu Cheng, Anqi Shi, Ya Zhao, Xiao Fang, Changmin Niu, Ying Zheng
{"title":"DNAI4 is required for flagellum assembly and male fertility in mice.","authors":"Fan Yang, Shiqi Meng, Wenting Lu, Jiayi Su, Guanghua Li, Tingting Ge, Yichun Zhao, Eoin C Whelan, Lu Yuan, Yueqi Yang, Fengming Zhang, Xu Cheng, Anqi Shi, Ya Zhao, Xiao Fang, Changmin Niu, Ying Zheng","doi":"10.1242/dev.205190","DOIUrl":"https://doi.org/10.1242/dev.205190","url":null,"abstract":"<p><p>Multiple morphological abnormalities of the sperm flagella (MMAF) is a major cause of male infertility, but identified gene mutations can only explain about 60% of clinical cases. Here, dynein axonemal intermediate chain 4 (DNAI4) is identified as an essential regulator of sperm flagellum morphogenesis. RT-PCR and western blot analyses indicate that expression of DNAI4 is enriched in murine testes. Dnai4 deletion in mice causes male-specific infertility due to oligoasthenoteratospermia with MMAF. Electron microscopy analyses revealed that DNAI4 deficiency resulted in an abnormal ultrastructure of sperm flagella, including disorganized mitochondrial sheaths, outer dense fibers, \"9+2\" axonemes, and missing inner dynein arms (IDA) and outer dynein arms. IDA component DNAH10 was remarkably reduced in testes and sperm tails of Dnai4 knockout mice. Immunoprecipitation demonstrated the interaction between DNAI4 and intraflagellar transport (IFT) 144 within the testes. Other IFT-A members including IFT140, IFT122 and IFT121 were down-regulated in sperm tails following Dnai4 deletion. Taken together, these findings establish DNAI4 as an essential regulator of sperm flagellum assembly and mammalian spermiogenesis, operating through the regulation of IDA assembly and retrograde IFT.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835107","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
Znhit1 mediated H2A.Z deposition governs transcriptional programs essential for oocyte meiotic progression. Znhit1介导H2A。Z沉积控制着卵母细胞减数分裂过程中必不可少的转录程序。
IF 3.6 2区 生物学
Development Pub Date : 2026-05-05 DOI: 10.1242/dev.205554
Na Fan, Hongyu Gong, Peijun Wang, Xue Bai, Xige He, Na Chen, Jiaying Gao, Haoran Li, Lu Wang, Gerile Naren, Fei Gao, Jiaojiao Guo, Tiemin Liu, Ning Jiang, Xinhua Lin, Xihe Li, Buhe Nashun
{"title":"Znhit1 mediated H2A.Z deposition governs transcriptional programs essential for oocyte meiotic progression.","authors":"Na Fan, Hongyu Gong, Peijun Wang, Xue Bai, Xige He, Na Chen, Jiaying Gao, Haoran Li, Lu Wang, Gerile Naren, Fei Gao, Jiaojiao Guo, Tiemin Liu, Ning Jiang, Xinhua Lin, Xihe Li, Buhe Nashun","doi":"10.1242/dev.205554","DOIUrl":"https://doi.org/10.1242/dev.205554","url":null,"abstract":"<p><p>Mammalian oogenesis is a precisely orchestrated developmental process, which depends on accurate chromatin remodeling and transcriptional regulation in the absence of DNA replication. The histone variant H2A.Z is required for oogenesis and embryogenesis, yet the chaperone directing its deposition has not been well characterized in mammalian oocytes. Here, we identify Znhit1, a core subunit of the SRCAP chromatin remodeling complex, as the essential factor mediating H2A.Z deposition in oocytes. Oocyte specific depletion of Znhit1 impairs H2A.Z incorporation and leads to severe ovarian phenotype, characterized by follicle loss, homologous chromosome segregation defects and meiotic arrest, which ultimately leads to female infertility. On molecular level, integrated Smart-seq2 and H2A.Z CUT&Tag analyses demonstrate that Znhit1 depletion severely reduces genome-wide H2A.Z deposition, particularly at promoter regions of key meiotic genes such as Aurkb, Tpm3, and Zar1, resulting in transcriptional dysregulation and aberrant meiotic gene expression. Our findings pinpoint Znhit1 as the histone chaperone essential for accurate deposition of histone variant H2A.Z ensuring meiotic progression and oocyte development in mice.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835148","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
Developmental dynamics of catshark cranial neural crest cells provide insights into gnathostome facial evolution. 猫鲨颅神经嵴细胞的发育动力学为颌面进化提供了新的见解。
IF 3.6 2区 生物学
Development Pub Date : 2026-05-01 Epub Date: 2026-05-07 DOI: 10.1242/dev.205258
Elio Escamilla-Vega, Andrea P Murillo-Rincón, Louk W G Seton, Ann-Katrin Koch, Stella Kyomen, Carsten Fortmann-Grote, Jörg U Hammel, Timo Moritz, Markéta Kaucká
{"title":"Developmental dynamics of catshark cranial neural crest cells provide insights into gnathostome facial evolution.","authors":"Elio Escamilla-Vega, Andrea P Murillo-Rincón, Louk W G Seton, Ann-Katrin Koch, Stella Kyomen, Carsten Fortmann-Grote, Jörg U Hammel, Timo Moritz, Markéta Kaucká","doi":"10.1242/dev.205258","DOIUrl":"10.1242/dev.205258","url":null,"abstract":"<p><p>Cranial neural crest cells (CNCCs) are a vertebrate-specific, multipotent cell population central to facial morphogenesis and a cellular substrate for evolutionary change. Although core CNCC developmental programmes are deeply conserved, changes in their gene expression programmes and cell behaviour underlie both macroevolutionary transitions and microevolutionary adaptations. While CNCC biology has been well characterized in bony vertebrates, comparatively little is known about CNCC properties and the behaviour of their derivatives in cartilaginous fishes (Chondrichthyes). To address this gap, we investigate CNCC development in a representative chondrichthyan: the small-spotted catshark (Scyliorhinus canicula). By integrating high-resolution molecular and morphological analyses, we reveal how conserved developmental programmes are modulated in chondrichthyans to generate divergent facial morphologies. We show that the molecular toolkit of CNCC is largely conserved across jawed vertebrates, and the developmental divergence and lineage-specific differences arise from divergent behaviour of their ectomesenchymal derivatives. These findings establish a high-resolution reference of CNCC biology in Chondrichthyes and uncover the evolutionary origins of both shared and lineage-specific traits, offering key insights into the developmental and evolutionary processes shaping gnathostome facial diversity.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688777","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
Transitions in development - an interview with Fei Zhang. 发展中的转型——张飞访谈
IF 3.6 2区 生物学
Development Pub Date : 2026-05-01 Epub Date: 2026-05-07 DOI: 10.1242/dev.205732
{"title":"Transitions in development - an interview with Fei Zhang.","authors":"","doi":"10.1242/dev.205732","DOIUrl":"https://doi.org/10.1242/dev.205732","url":null,"abstract":"<p><p>Fei Zhang is a Professor at Huazhong Agricultural University in Wuhan, Hubei Province, China. Fei's group works on Citrus development, with a specific interest in shoot meristems, thorns and oil glands. We spoke to Fei to learn more about his career trajectory, lessons from previous mentors and the importance of relaxation in science.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"153 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834077","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
Progressive correction of auditory hair cell orientation in the absence of core planar cell polarity and GPR156 signaling. 在核心平面细胞极性和GPR156信号缺失的情况下,听觉毛细胞定向的渐进式校正。
IF 3.6 2区 生物学
Development Pub Date : 2026-05-01 DOI: 10.1242/dev.205332
Amandine Jarysta, Justin Nemelka, Muthumeena Ramanathan, Ellison J Goodrich, Brianna L Vonderhaar, Sungjin Park, Cesare Orlandi, Michael R Deans, Basile Tarchini
{"title":"Progressive correction of auditory hair cell orientation in the absence of core planar cell polarity and GPR156 signaling.","authors":"Amandine Jarysta, Justin Nemelka, Muthumeena Ramanathan, Ellison J Goodrich, Brianna L Vonderhaar, Sungjin Park, Cesare Orlandi, Michael R Deans, Basile Tarchini","doi":"10.1242/dev.205332","DOIUrl":"https://doi.org/10.1242/dev.205332","url":null,"abstract":"<p><p>Planar cell polarity (PCP) proteins, including Van Gogh-like and Frizzled, orient sensory hair cells in the inner ear. Because most PCP mouse models die at birth, orientation defects have been studied mainly at fetal stages. Using viable conditional mutants lacking both Vangl1/Vangl2 or Frizzled3/Frizzled6, we show that misoriented auditory hair cells undergo extensive postnatal reorientation, largely correcting defects over time. These findings extend previous observations in Vangl2 single conditional mutants and demonstrate that correction does not require redundant core PCP partners. GPR156, a receptor that reverses how PCP signaling is interpreted in some hair cell types, is also essential for orientation but Gpr156 mutants fail to correct defects. We therefore tested its role in core PCP mutant recovery. GPR156 binds and depends on VANGL proteins, yet inhibiting GPR156 signaling facilitates rather than prevents correction in Vangl and Frizzled mutants. Thus, GPR156 collaborates with core PCP components to establish hair cell orientation but is dispensable-and even inhibitory-for postnatal realignment. These findings reveal extensive plasticity in hair cell orientation and identify GPR156 as a context-dependent partner of core PCP proteins.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812519","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
Oscillatory co-expression of HES1 and HES5 Enables a hybrid state in a cross-repressive transcription factor regulatory motif. HES1和HES5的振荡共表达使交叉抑制转录因子调控基序的杂交状态成为可能。
IF 3.6 2区 生物学
Development Pub Date : 2026-05-01 DOI: 10.1242/dev.204969
Veronica Biga, Anzy Miller, Anoushka Kamath, Robert Lea, Ying Q P Mak, Antony D Adamson, Elli Marinopoulou, Paul François, Nancy Papalopulu, Cerys S Manning
{"title":"Oscillatory co-expression of HES1 and HES5 Enables a hybrid state in a cross-repressive transcription factor regulatory motif.","authors":"Veronica Biga, Anzy Miller, Anoushka Kamath, Robert Lea, Ying Q P Mak, Antony D Adamson, Elli Marinopoulou, Paul François, Nancy Papalopulu, Cerys S Manning","doi":"10.1242/dev.204969","DOIUrl":"https://doi.org/10.1242/dev.204969","url":null,"abstract":"<p><p>Many cell fate decisions in the developing neural tube are directed by cross-repressive transcription factor (TF) motifs that generate bistability, such that cells express one TF but not both. Hybrid states in which cells express both cross-repressing fate determinants have been observed, but how these arise or persist remains unclear. Here, we focus on HES1 and HES5, auto-repressive, oscillatory TFs that regulate neural progenitor maintenance and are expressed in adjacent dorsoventral progenitor domains in the developing spinal cord. Knockdown experiments demonstrate that HES1 and HES5 are cross-repressing in mouse spinal cord neural progenitors, and live-cell imaging in vitro shows that they can be co-expressed, defining a hybrid state. In this state, HES co-oscillate in-phase within single cells. Computational modelling indicates that modulation of cross-repression strength or relative TF abundance destabilises this state, driving resolution towards a single oscillatory HES TF. This is consistent with in vivo analysis showing transient HES1/HES5 co-expression followed by progressive restriction to a single TF oscillator. Our findings suggest that oscillatory expression enables co-existence of cross-repressing TFs, allowing hybrid states within a developmental bistable motif.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812608","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
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