DevelopmentPub Date : 2025-03-15Epub Date: 2025-03-27DOI: 10.1242/dev.204585
Laura L Thomas, Devavrat M Bodas, Geraldine Seydoux
{"title":"FG repeats drive co-clustering of nuclear pores and P granules in the C. elegans germline.","authors":"Laura L Thomas, Devavrat M Bodas, Geraldine Seydoux","doi":"10.1242/dev.204585","DOIUrl":"10.1242/dev.204585","url":null,"abstract":"<p><p>Condensates that accumulate small RNA biogenesis factors (nuage) are common in germ cells and often associate with nuclei. In the Caenorhabditis elegans germline, P granules overlay large clusters of nuclear pores and this organization has been proposed to facilitate surveillance of nascent transcripts by Argonaute proteins enriched in P granules. We report that co-clustering of nuclear pores and P granules depends on FG repeat-containing nucleoporins and FG repeats in the Vasa class helicase GLH-1. Worms with mutations that prevent this co-clustering are fertile under standard growth conditions and exhibit misregulation of only a minority of genes, including replication-dependent histones. Our observations suggest that association with nuclear pores, although non-essential for genome surveillance, may serve to tune mRNA flow through P granules and other nuage condensates.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604218","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 : 2025-03-15Epub Date: 2025-03-21DOI: 10.1242/dev.204289
Yanfeng Li, You Li, Bangzhuo Huang, Ruhao Zhang, Jianbo He, Lingfei Luo, Yun Yang
{"title":"Long-term labelling and tracing of endodermal cells using a perpetual cycling Gal4-UAS system.","authors":"Yanfeng Li, You Li, Bangzhuo Huang, Ruhao Zhang, Jianbo He, Lingfei Luo, Yun Yang","doi":"10.1242/dev.204289","DOIUrl":"10.1242/dev.204289","url":null,"abstract":"<p><p>Cell labelling and lineage tracing are indispensable tools in developmental biology, offering powerful means with which to visualise and understand the complex dynamics of cell populations during embryogenesis. Traditional cell labelling relies heavily on signal stability, promoter strength and stage specificity, limiting its application in long-term tracing. In this report, we optimise and reconfigure a perpetual cycling Gal4-UAS system employing a previously unreported Gal4 fusion protein and the autoregulatory Gal4 expression loop. As validated through heat-shock induction, this configuration ensures sustained transcription of reporter genes in target cells and their descendant cells while minimising cytotoxicity, thereby achieving long-term labelling and tracing. Further exploiting this system, we generate zebrafish transgenic lines with continuous fluorescent labelling specific to the endoderm, and demonstrate its effectiveness in long-term tracing by showing the progression of endoderm development from embryo to adult, providing visualisation of endodermal cells and their derived tissues. This continuous labelling and tracing strategy can span the entire process of endodermal differentiation, from progenitor cells to mature functional cells, and is applicable to studying endoderm patterning and organogenesis.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669395","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 : 2025-03-15Epub Date: 2025-03-26DOI: 10.1242/dev.204787
{"title":"The people behind the papers - Laura Lahti and Thomas Perlmann.","authors":"","doi":"10.1242/dev.204787","DOIUrl":"https://doi.org/10.1242/dev.204787","url":null,"abstract":"<p><p>Midbrain dopamine (mDA) neuron degeneration is a major cause of Parkinson's disease, so understanding the mechanisms underpinning mDA neuron production could help inform future treatments. A new paper in Development identifies key transcription factors that regulate the timing of cell cycle exit in mDA progenitors. The study also identifies a population of ependymal cells that exhibit progenitor potential. To learn more about the story behind the paper, we caught up with first author Laura Lahti and corresponding author Thomas Perlmann, Professor in Molecular Developmental Biology at the Karolinska Institute, Sweden.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709382","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 : 2025-03-15Epub Date: 2025-03-26DOI: 10.1242/dev.204421
Laura Lahti, Nikolaos Volakakis, Linda Gillberg, Behzad Yaghmaeian Salmani, Katarína Tiklová, Nigel Kee, Hilda Lundén-Miguel, Maarten Werkman, Michael Piper, Richard Gronostajski, Thomas Perlmann
{"title":"Sox9 and nuclear factor I transcription factors regulate the timing of neurogenesis and ependymal maturation in dopamine progenitors.","authors":"Laura Lahti, Nikolaos Volakakis, Linda Gillberg, Behzad Yaghmaeian Salmani, Katarína Tiklová, Nigel Kee, Hilda Lundén-Miguel, Maarten Werkman, Michael Piper, Richard Gronostajski, Thomas Perlmann","doi":"10.1242/dev.204421","DOIUrl":"10.1242/dev.204421","url":null,"abstract":"<p><p>Correct timing of neurogenesis is crucial for generating the correct number and subtypes of glia and neurons in the embryo, and for preventing tumours and stem cell depletion in the adults. Here, we analyse how the midbrain dopamine (mDA) neuron progenitors transition into cell cycle arrest (G0) and begin to mature into ependymal cells. Comparison of mDA progenitors from different embryonic stages revealed upregulation of the genes encoding Sox9 and nuclear factor I transcription factors during development. Their conditional inactivation in the early embryonic midbrain led to delayed G0 entry and ependymal maturation in the entire midbrain ventricular zone, reduced gliogenesis and increased generation of neurons, including mDA neurons. In contrast, their inactivation in late embryogenesis did not result in mitotic re-entry, suggesting that these factors are necessary for G0 induction, but not for its maintenance. Our characterisation of adult ependymal cells by single-cell RNA sequencing and histology show that mDA-progenitor-derived cells retain several progenitor features but also secrete neuropeptides and contact neighbouring cells and blood vessels, indicating that these cells may form part of the circumventricular organ system.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490469","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 : 2025-03-15Epub Date: 2025-03-31DOI: 10.1242/dev.204706
Virginia L Pimmett, James McGehee, Antonio Trullo, Maria Douaihy, Ovidiu Radulescu, Angelike Stathopoulos, Mounia Lagha
{"title":"Optogenetic manipulation of nuclear Dorsal reveals temporal requirements and consequences for transcription.","authors":"Virginia L Pimmett, James McGehee, Antonio Trullo, Maria Douaihy, Ovidiu Radulescu, Angelike Stathopoulos, Mounia Lagha","doi":"10.1242/dev.204706","DOIUrl":"10.1242/dev.204706","url":null,"abstract":"<p><p>Morphogen gradients convey essential spatial information during tissue patterning. Although the concentration and timing of morphogen exposure are both crucial, how cells interpret these graded inputs remains challenging to address. We employed an optogenetic system to acutely and reversibly modulate the nuclear concentration of the morphogen Dorsal (DL), homolog of NF-κB, which orchestrates dorsoventral patterning in the Drosophila embryo. By controlling DL nuclear concentration while simultaneously recording target gene outputs in real time, we identified a critical window for DL action that is required to instruct patterning and characterized the resulting effect on spatiotemporal transcription of target genes in terms of timing, coordination and bursting. We found that a transient decrease in nuclear DL levels at nuclear cycle 13 leads to reduced expression of the mesoderm-associated gene snail (sna) and partial derepression of the neurogenic ectoderm-associated target short gastrulation (sog) in ventral regions. Surprisingly, the mispatterning elicited by this transient change in DL was detectable at the level of single-cell transcriptional bursting kinetics, specifically affecting long inter-burst durations. Our approach of using temporally resolved and reversible modulation of a morphogen in vivo, combined with mathematical modeling, establishes a framework for understanding the stimulus-response relationships that govern embryonic patterning.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522788","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":"Dynamic interactions between cartilaginous and tendinous/ligamentous primordia during musculoskeletal integration.","authors":"Xinyi Yu, Ryosuke Kawakami, Shinsei Yambe, Yuki Yoshimoto, Takako Sasaki, Shinnosuke Higuchi, Hitomi Watanabe, Haruhiko Akiyama, Shigenori Miura, Kadi Hu, Gen Kondoh, Ramu Sagasaki, Masafumi Inui, Taiji Adachi, Denitsa Docheva, Takeshi Imamura, Chisa Shukunami","doi":"10.1242/dev.204512","DOIUrl":"https://doi.org/10.1242/dev.204512","url":null,"abstract":"<p><p>Proper connections between cartilaginous and muscular primordia through tendinous/ligamentous primordia are essential for musculoskeletal integration. Herein, we report a novel double-reporter mouse model for investigating this process via fluorescently visualising scleraxis (Scx) and SRY-box containing gene 9 (Sox9) expression. We generated ScxTomato transgenic mice and crossed them with Sox9EGFP knock-in mice to obtain ScxTomato;Sox9EGFP mice. Deep imaging of optically cleared double-reporter embryos at E13.5 and E16.5 revealed previously unknown differences in the dynamic interactions between cartilaginous and tendinous/ligamentous primordia in control and Scx-deficient mice. Tendon/ligament maturation was evaluated through simultaneous detection of fluorescence and visualisation of collagen fibre formation using second harmonic generation imaging. Lack of deltoid tuberosity in Scx-deficient mice caused misdirected muscle attachment with morphological changes. Loss of Scx also dysregulated progenitor cell fate determination in the chondrotendinous junction, resulting in the formation of a rounded enthesis rather than the protruding enthesis observed in the control. Hence, our double-reporter mouse system, in combination with loss- or gain-of-function approaches, is a unique and powerful tool that could be used to gain a comprehensive understanding of musculoskeletal integration.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709378","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 : 2025-03-15Epub Date: 2025-03-19DOI: 10.1242/dev.204730
Lucas Leclère, Chiara Sinigaglia
{"title":"In preprints: the ins and outs of Cnidaria germ layers.","authors":"Lucas Leclère, Chiara Sinigaglia","doi":"10.1242/dev.204730","DOIUrl":"https://doi.org/10.1242/dev.204730","url":null,"abstract":"","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662654","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 : 2025-03-15Epub Date: 2025-03-13DOI: 10.1242/dev.204757
James Briscoe, Craig E Franklin, Daniel A Gorelick, E Elizabeth Patton, Michael Way
{"title":"Science under siege: protecting scientific progress in turbulent times.","authors":"James Briscoe, Craig E Franklin, Daniel A Gorelick, E Elizabeth Patton, Michael Way","doi":"10.1242/dev.204757","DOIUrl":"https://doi.org/10.1242/dev.204757","url":null,"abstract":"","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623938","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":"The KMT2 complex protein ASH2L is required for meiotic prophase progression but dispensable for mitosis in differentiated spermatogonia.","authors":"Zhen Lin, Bowen Rong, Meixia Wu, Junyi Yan, Tong Hong, Linjun Hou, Xinzhe Tang, Qiang Liu, Xiaozhong Peng, Yao Chen, Fei Lan, Ming-Han Tong","doi":"10.1242/dev.204630","DOIUrl":"10.1242/dev.204630","url":null,"abstract":"<p><p>ASH2L is a core component of KMT2 complexes, crucial for H3K4 trimethylation. However, its role in spermatogenesis remains elusive. Here, we demonstrate an essential role of Ash2l for meiotic prophase but dispensable for mitosis in differentiated spermatogonia. Using a germ cell-specific Ash2l knockout mouse model, we reveal that Ash2l deficiency leads to meiotic arrest and sterility in both sexes. Ash2l-deficient spermatocytes exhibit failures in chromosomal synapsis associated with persistent DMC1 foci and γH2AX, resulting in meiocyte loss due to apoptosis. Conversely, Ash2l-deficient differentiated spermatogonia show normal development. Mechanistically, Ash2l deficiency results in a global loss of H3K4me3 in promoter regions and significantly decreases expression of thousands of genes. Among these are genes involved in epigenetic silencing pathways, such as H3K9 di-methylation, DNA methylation and piRNA pathways, that are crucial for transposon repression during meiotic prophase I progression. Supporting this, we observe that Ash2l mutant spermatocytes display ectopic expression of LINE1-ORF1P. Our findings therefore reveal the previously unappreciated role of ASH2L-dependent H3K4me3 modification in spermatogenesis and provide clues to the molecular mechanisms in epigenetic disorders underlying male infertility.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482527","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}