bioRxiv - Developmental Biology最新文献

{"title":"Microtubules coordinate mitochondria transport with myofibril morphogenesis during muscle development","authors":"Jerome Avellaneda, Duarte Candeias, Ana da Rosa Soares, Edgar R. Gomes, Nuno Miguel Luis, Frank Schnorrer","doi":"10.1101/2024.09.16.613277","DOIUrl":"https://doi.org/10.1101/2024.09.16.613277","url":null,"abstract":"Muscle morphogenesis creates highly specialised muscle cells containing contractile myofibrils and energy producing mitochondria. Myofibrils are chains of sarcomeres, whose myosin motors slide over actin filaments at the expense of ATP. Thus, myofibrils and mitochondria are in intimate contact in mature muscles. However, how mitochondria morphogenesis is coordinated with myofibrillogenesis during development remains largely unknown. Here, we used in vivo imaging to investigate myofibril and mitochondria network dynamics in developing Drosophila flight muscles. We found that mitochondria rapidly intercalate from the surface of actin bundles to their interior; concomitantly, actin filaments condense to individual myofibrils. This ensures that mitochondria are in intimate proximity to each myofibril. Interestingly, antiparallel microtubules bundle in concert with the assembling myofibrils, suggesting a key role in myofibril orientation. Indeed, light-induced microtubule severing directly affects myofibril orientation, whereas knock-down of kinesin heavy chain specifically blocks mitochondria intercalation and long-range transport. Importantly, mitochondria-myofibril intercalation and microtubule-based transport of mitochondria is conserved in developing mammalian muscle. Together, these data identify a key role for microtubules in coordinating mitochondria and myofibril morphogenesis to build functional muscles.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NR2F2 regulation of interstitial to fetal Leydig cell differentiation in the testis: insights into differences of sex development","authors":"Martin Andres Estermann, Sara Grimm, Abigail Kitakule, Karina Flores Rodriguez, Paula Brown, Kathryn McClelland, Ciro Maurizio Amato, Humphrey Hung-Chang Yao","doi":"10.1101/2024.09.16.613312","DOIUrl":"https://doi.org/10.1101/2024.09.16.613312","url":null,"abstract":"Testicular fetal Leydig cells are a specialized cell type responsible for embryo masculinization. Fetal Leydig cells produce androgens, that induce the differentiation of male reproductive system and sexual characteristics. Deficiencies in Leydig cell differentiation leads to various disorders of sex development and male reproductive defects such as ambiguous genitalia, hypospadias, cryptorchidism, and infertility. Fetal Leydig cells are thought to originate from proliferating progenitor cells in the testis interstitium, marked by genes like Arx, Pdgfra, Tcf21 and Wnt5a. However, the precise mechanisms governing the transition from interstitial cells to fetal Leydig cells remain elusive. Through integrated approaches involving mouse models and single-nucleus multiomic analyses, we discovered that fetal Leydig cells originate from a Nr2f2-positive non-steroidogenic interstitial cell population. Embryonic deletion of Nr2f2 in mouse testes resulted in disorders of sex development, including dysgenic testes, Leydig cell hypoplasia, cryptorchidism, and hypospadias. We found that NR2F2 promotes the progenitor cell fate while suppresses Leydig cell differentiation by directly and indirectly controlling a cohort of transcription factors and downstream genes. Bioinformatic analyses of single-nucleus ATAC-seq and NR2F2 ChIP-seq data revealed putative transcription factors co-regulating the process of interstitial to Leydig cell differentiation. Collectively, our findings not only highlight the critical role of Nr2f2 in orchestrating the transition from interstitial cells to fetal Leydig cells, but also provide molecular insight into the disorders of sex development as a result of Nr2f2 mutations.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanical coupling of compartments drives polarity and patterning of mouse auditory epithelium","authors":"Anubhav Prakash, Sukanya Raman, Raman Kaushik, Anton S Iyer, Raj K Ladher","doi":"10.1101/2024.09.16.613243","DOIUrl":"https://doi.org/10.1101/2024.09.16.613243","url":null,"abstract":"The information that drives morphogenesis depends not only on genetically encoded cellular properties, but also emerges from the interaction between these cell behaviours. This information is spatio-temporally implemented to make tissue shape and order robust and reproducible during development. What are the principles for organising this information? The mouse auditory epithelium, the organ of Corti (OC) is an excellent system to investigate this. A central domain senses sound information through mechanosensory hair cells (HC), part of a mosaic with supporting cells (SC). This is flanked by non-sensory domains. These domains undergo cellular rearrangements as they become ordered and elongate. How cellular properties are coordinated across domains and how these contribute to tissue shape is unknown. Here, we find adhesion codes, established through morphogen patterning, define OC domains as compartments. Cells in each compartment exhibit distinct patterns of ordering. By perturbing cellular rearrangements in individual compartments, we find that compartment-specific ordering can contribute to overall tissue architecture. Perturbation of cell order within a compartment also affects the organisation in another. Using vinculin mutants, we show that inter-compartment coupling is, in part, mechanical. Our work suggests that compartments and their coupling can organise morphogenetic information in space and time during organogenesis.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YAP/TAZ signaling in allantois-derived cells is required for placental vascularization","authors":"Siqi Gao, Triloshan Thillaikumaran, Martin H Dominguez, William Giang, Kevin Hayes, Xiaowen Chen, Jesse Pace, Jenna Bockman, Danielle Jathan, Derek C Sung, Sweta Narayan, Maxwell Frankfurter, Mei Chen, Patricia Mericko, Jisheng Yang, Marco Castro, Michael Potente, Mark Kahn","doi":"10.1101/2024.09.15.613151","DOIUrl":"https://doi.org/10.1101/2024.09.15.613151","url":null,"abstract":"Normal placental development and angiogenesis are crucial for fetal growth and maternal health during pregnancy. However, molecular regulation of placental angiogenesis has been difficult to study due to a lack of specific genetic tools that isolate the placenta from the embryo and yolk sac. To address this gap in knowledge we recently developed Hoxa13Cre mice in which Cre is expressed in allantois-derived cells, including placental endothelial and stromal cells. Mice lacking the transcriptional regulators Yes-associated protein (YAP) and PDZ-binding motif (TAZ) in allantois-derived cells exhibit embryonic lethality at midgestation with compromised placental vasculature. snRNA-seq analysis revealed transcriptional changes in placental stromal cells and endothelial cells. YAP/TAZ mutants exhibited significantly reduced placental stromal cells prior to the endothelial architectural change, highlighting the role of these cells in placental vascular growth. These results reveal a central role for YAP/TAZ signaling during placental vascular growth and implicate Hoxa13-derived placental stromal cells as a critical component of placental vascularization.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Notch and LIM-homeodomain protein Arrowhead regulate each other in a feedback mechanism to play a role in wing and neuronal development in Drosophila","authors":"Jyoti Singh, Dipti Verma, Bappi Sarkar, Maimuna Sali Paul, Mousumi Mutsuddi, Ashim Mukherjee","doi":"10.1101/2024.09.16.613220","DOIUrl":"https://doi.org/10.1101/2024.09.16.613220","url":null,"abstract":"Notch pathway is an evolutionarily conserved signaling system that operates to influence an astonishing array of cell fate decisions in different developmental contexts. To identify novel effectors of Notch signaling, we analyzed the whole transcriptome of Drosophila wing and eye imaginal discs in which an activated form of Notch was overexpressed. A LIM homeodomain protein Arrowhead (Awh) was identified as a novel candidate which plays a crucial role in Notch mediated developmental events. Awh alleles show strong genetic interaction with Notch pathway components. Awh loss-of-function upregulates Notch targets Cut and Wingless. Awh gain-of-function downregulates Notch targets by reducing the expression of ligand, Delta. Consequently, the expression of Wingless effector molecule Armadillo and its downstream targets, Senseless and Vestigial, also gets downregulated. Awh overexpression leads to ectopic expression of engrailed, a segment polarity gene in the anterior region of wing disc, leading to patterning defects. Additionally, Notch gain-of-function mediated neuronal defects get significantly rescued with Awh overexpression. Activated Notch inhibits Awh activity, suggesting a regulatory loop between Awh and Notch. Additionally, the defects caused by Awh gain-of-function were remarkably rescued by Chip, a LIM interaction domain containing transcriptional co-factor. The present study highlights the novel feedback regulation between Awh and Notch.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ca2+-evoked sperm cessation determines embryo number in mammals.","authors":"Hitomi Watanabe, Daiya Ohara, Shinichiro Chuma, Yusuke Takeuchi, Tomoatsu Takano, Ami Katanaya, Satohiro Nakao, Akihisa Kaneko, Takatoku Oida, Tatsuya Katsuno, Takuya Uehata, Toru Takeo, Munehiro Okamoto, Keiji Hirota, Gen Kondoh","doi":"10.1101/2024.09.16.613169","DOIUrl":"https://doi.org/10.1101/2024.09.16.613169","url":null,"abstract":"In mammals, fertilization takes place followed by fetus development in the maternal body, so the number of fetuses that exceeds the mother's capacity increases the frequency of stunted growth and stillbirths, while an excessive number of pups increases postnatal stunting and maternal child-rearing stress, which is detrimental to offspring procreation and species maintenance. Therefore, various control mechanisms are thought to be at work to ensure that fertilization occurs in appropriate numbers. Sperm are not capable of fertilization immediately after they are produced in the testis, and must undergo a stepwise activation process including capacitation, hyper motility activation or acrosome reaction before they meet the egg in the oviduct, where fertilization takes place, contributing positively on fertilization, which in turn ensures the number of fetuses for the maintenance of species. In contrast, in this study, we found that a subpopulation of sperm is derived in a Ca2+-dependent manner during the process for sperm to acquire fertility, which may regulate the number of fetuses. When sperm were harvested from the epididymis of mice and activated in vitro, a subpopulation of sperm emerged from the sperm population in which Lypd4 was expressed on the sperm surface at a ratio up to 30%. The sperm in this subpopulation were rather small in size, more permeable to dyes, and had already ceased motility. We further characterized this sperm population by surface antigen screening using various monoclonal antibodies and found the expression of several proteins, such as CD55, ICOS or Ccr3, specific to this population. The emergence of this sperm population was induced at a concentration of about 4% of Ca2+ in body fluids and was independent of capacitation or acrosome reaction, and also apoptotic process. This subpopulation also appeared over time in sperm ejaculated into the female body, accounting for about 50% of the sperm that reached the oviduct in an hour. When this sperm subpopulation was then removed from the entire population using anti-Lypd4 antibody followed by in utero insemination, the fertilization rate of the oocytes collected from the oviducts doubled. Such a sperm subpopulation was also observed in macaque monkeys, and removal of this subpopulation increased the egg penetration rate of sperm, suggesting that this sperm subpopulation exists commonly in mammals and that the mother's acceptable fetal number is adjusted by systematically sterilizing a certain number of sperm.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Somatic Transthyretin-Related Proteins in C. elegans Govern Reproductive Longevity by Sustaining Sperm Integrity and Timely Ovulation","authors":"Tingshan Wu, Haochen Lyu, Zhao Wang, Zhaoyang Jiang, Yingchuan B. Qi","doi":"10.1101/2024.09.13.612966","DOIUrl":"https://doi.org/10.1101/2024.09.13.612966","url":null,"abstract":"The decline in reproductive capability during adult life is critical for health, but its mechanism is elusive. We systematically analyzed the developmental role of an expanded TTR family of proteins, structurally analogous to mammalian thyroid hormone-transporting Transthyretin, and identified three paralogous proteins, TTR-15, TTR-16, and TTR-17, differentially expressed in somatic cells of the gonads and secreted around gametes in C. elegans. Simultaneous inactivation of TTR-15, TTR-16, and TTR-17 leads to a rapid reduction in reproductive capacity in middle age. While oocyte and sperm production remain unaffected in the triple mutants, late-onset infertility results from stalled ovulation. Mechanistically, the absence of TTR-15, TTR-16, and TTR-17 causes sperm to prematurely deplete the cytoplasmic pool of major sperm protein (MSP), released via non-conventional vesicle budding as a signal for ovulation. We propose that the somatic gonads play a central role in maintaining sperm integrity post-production and determining the duration of the reproductive age.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-transcriptional RNA processing boosts zygotic gene activation","authors":"Jingzhao Xu, Xiaojing Li, Xiaowen Hao, Xinyun Hu, Shaoqian Ma, Yantao Hong, Jing Zhang, Dingfei Yan, Haiteng Deng, Jie Na, Xiong Ji, Zai Chang, Xiaohua Shen","doi":"10.1101/2024.09.14.613088","DOIUrl":"https://doi.org/10.1101/2024.09.14.613088","url":null,"abstract":"Transcription decodes protein-coding genes and interprets regulatory information embedded in the genome by generating RNA. In eukaryotes, gene transcription is coupled with RNA processing via the carboxyl terminal domain (CTD) of RNA polymerase (Pol) II, which enhances messenger RNA (mRNA) production. We propose that co-transcriptional RNA processing is essential for zygotic gene activation (ZGA), transitioning the transcription program from noncoding to protein-coding after fertilization. Truncating the CTD in mouse cells disrupts this coupling, halting global mRNA synthesis and increasing noncoding RNA (ncRNA) levels through enhanced intergenic transcription and RNA stabilization. CTD truncation also triggers epigenetic reprogramming and nuclear reorganization towards totipotency, resembling early cleavage embryos. Mechanistically, the CTD restrains nonproductive polymerase activity in noncoding sequences, while at protein-coding genes requiring RNA processing, it promotes elongation by facilitating polymerase promoter-proximal pausing, transcription directionality, and velocity. Longer CTD lengths enhance gene activity, likely evolving to accommodate the increasing noncoding sequences in mammalian genomes.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ARHGEF3 Regulates Hair Follicle Morphogenesis","authors":"Krithika Kalyanakrishnan, Amy Beaudin, Alexandra Jette, Sarah Ghezelbash, Diana Ioana Hotea, Jie Chen, Philippe Lefrancois, Melanie Laurin","doi":"10.1101/2024.09.13.612256","DOIUrl":"https://doi.org/10.1101/2024.09.13.612256","url":null,"abstract":"During embryogenesis, cells arrange into precise patterns that enable tissues and organs to develop specialized functions. Despite its critical importance, the molecular choreography behind these collective cellular behaviors remains elusive, posing a major challenge in developmental biology and limiting advances in regenerative medicine. By using the mouse hair follicle as a mini-organ system to study the formation of bud-like structures during embryonic development, our work uncovers a crucial role for the Rho GTPase regulator ARHGEF3 in hair follicle morphogenesis. We demonstrate that Arhgef3 expression is upregulated at the onset of hair follicle placode formation. In Arhgef3 knockout animals, we observed defects in placode cell compaction, leading to impaired hair follicle downgrowth. Through cell culture models, we show that ARHGEF3 promotes F-actin accumulation at the cell cortex and P-cadherin enrichment at cell-cell junctions. Collectively, our study identifies ARHGEF3 as a new regulator of cell shape rearrangements during hair placode morphogenesis, warranting further exploration of its role in other epithelial appendages that arise from similar developmental processes.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The microbiota extends the reproductive lifespan by safeguarding the ovarian reserve","authors":"Sarah K Munyoki, Julie P Goff, Amanda Reshke, Erin Wilderoter, Nyasha Mafarachisi, Antonija Kolobaric, Yi Sheng, Steven Mullett, Gabrielle King, Jacob DeSchepper, Richard Bookser, Carlos A Castro, Stacy Gelhaus, Mayara Grizotte-Lake, Kathleen E Morrison, Anthony J Zeleznik, Timothy W Hand, Miguel Brieno-Enriquez, Eldin Jasarevic","doi":"10.1101/2024.09.13.612929","DOIUrl":"https://doi.org/10.1101/2024.09.13.612929","url":null,"abstract":"Infertility is a devastating condition affecting one in six people globally. In many cases, the underlying causes are unknown. Emerging evidence suggests that the microbiota influences reproduction, yet the mechanistic link between the microbiota, ovarian function, and length of the fertile lifespan remain unexplored. Here we report that the microbiota controls the length of the reproductive lifespan by maintaining the primordial follicle pool, a process mediated by microbiota-derived short chain fatty acids modulating gene regulatory networks crucial for the survival of the ovarian reserve. Dietary perturbation of the microbiota during a critical developmental window is sufficient to diminish the ovarian reserve, reduce oocyte retrieval, and impair preimplantation embryo viability, mirroring challenges in human fertility treatments. Targeted interventions to restore microbiota improve assisted reproductive outcomes, particularly when implemented early. These findings reveal a novel contribution of host-microbe interactions in mammalian reproduction and demonstrate that the microbiota impacts ovarian function and fertility.","PeriodicalId":501269,"journal":{"name":"bioRxiv - Developmental Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}