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Injury-induced Neuregulin-EGFR signaling from muscle mobilizes stem cells for whole-body regeneration in acoels 肌肉损伤诱导的神经调节蛋白egfr信号可动员干细胞进行全身再生。
IF 2.1 3区 生物学
Developmental biology Pub Date : 2025-09-06 DOI: 10.1016/j.ydbio.2025.08.024
Brian Stevens , Riley Popp , Heather Valera , Kyle Krueger , Christian P. Petersen
{"title":"Injury-induced Neuregulin-EGFR signaling from muscle mobilizes stem cells for whole-body regeneration in acoels","authors":"Brian Stevens ,&nbsp;Riley Popp ,&nbsp;Heather Valera ,&nbsp;Kyle Krueger ,&nbsp;Christian P. Petersen","doi":"10.1016/j.ydbio.2025.08.024","DOIUrl":"10.1016/j.ydbio.2025.08.024","url":null,"abstract":"<div><div>The activation of progenitor cells near wound sites is a common feature of regeneration across species, but the conserved signaling mechanisms responsible for this step in whole-body regeneration are still incompletely understood. The acoel <em>Hofstenia miamia</em> undergoes whole-body regeneration using Piwi + pluripotent adult stem cells (neoblasts) that accumulate at amputation sites early in regeneration. The EGFR signaling pathway has broad roles in controlling proliferation, migration, differentiation, and cell survival across metazoans. Using candidate RNAi screening, we identify the <em>Hofstenia</em> EGFR <em>egfr-1</em> and Neuregulin <em>nrg-1</em> genes as essential for blastema formation. Structure prediction of NRG-1 and EGFR-1 proteins suggests these factors interact directly. After amputation injuries, <em>nrg-1</em> expression is induced in body-wall muscle cells at the wound site by 6 h and localizes to the tip of the outgrowing blastema by 24 h and sustains for several days, while <em>egfr-1</em> is broadly expressed, including in muscle and neoblasts. The early phase of <em>nrg-1</em> expression occurs at incision sites that repair through wound healing while the late phase is specific to blastema formation. Under <em>nrg-1(RNAi)</em> and <em>egfr-1(RNAi)</em> conditions that impair blastema formation, animals still undergo the earliest responses to injury to activate expression of the Early Growth Response transcription factor <em>egr</em>. In addition, RNAi of <em>nrg-1</em> only after amputation results in regeneration failure, indicating regeneration requires new <em>nrg-1</em> expression. <em>nrg-1(RNAi)</em> and <em>egfr-1(RNAi)</em> animals possess Piwi+ and H3P + mitotic neoblasts which hyperproliferate normally after amputation, but these cells fail to accumulate at the wound site. Therefore, muscle provides a source for Neuregulin-EGFR signaling after injury and is necessary for the mobilization of proliferative progenitors to enable blastema outgrowth for whole-body regeneration in <em>Hofstenia</em>. These results indicate a shared functional requirement for muscle signaling to enable regeneration between planarians and acoels across 550 million years of evolution.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 105-116"},"PeriodicalIF":2.1,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
CXXC Finger Protein 1 drives BMP signaling and progenitor cell differentiation during limb development CXXC手指蛋白1在肢体发育过程中驱动BMP信号传导和祖细胞分化。
IF 2.1 3区 生物学
Developmental biology Pub Date : 2025-09-05 DOI: 10.1016/j.ydbio.2025.09.004
Emanuele Pignatti , Lijie Jiang , Manasvi S. Shah , Anish Karpurapu , Ji Miao , Yangyang Liu , Mesut Berber , Roshini Kalagara , Aisling E. Butler , David G. Skalnik , Vicki Rosen , David T. Breault , Diana L. Carlone
{"title":"CXXC Finger Protein 1 drives BMP signaling and progenitor cell differentiation during limb development","authors":"Emanuele Pignatti ,&nbsp;Lijie Jiang ,&nbsp;Manasvi S. Shah ,&nbsp;Anish Karpurapu ,&nbsp;Ji Miao ,&nbsp;Yangyang Liu ,&nbsp;Mesut Berber ,&nbsp;Roshini Kalagara ,&nbsp;Aisling E. Butler ,&nbsp;David G. Skalnik ,&nbsp;Vicki Rosen ,&nbsp;David T. Breault ,&nbsp;Diana L. Carlone","doi":"10.1016/j.ydbio.2025.09.004","DOIUrl":"10.1016/j.ydbio.2025.09.004","url":null,"abstract":"<div><div>The mechanisms mediating endochondral bone formation remain incompletely understood. Here, we show that CXXC Finger Protein 1 (CFP1) is required for the onset of chondrogenesis during forelimb development. CFP1-deficient mesenchymal progenitor cells (LMPs) retain an immature molecular signature with elevated FGF and SHH signaling and repressed BMP signaling, in part, due to (1) reduced expression of type I BMP receptors, (2) reduced Smad1 protein levels and (3) an altered extracellular niche. Moreover, the addition of exogenous BMP ligand or antagonism of heparan sulfate restores LMP differentiation toward a chondrogenic fate and enhances BMP signaling, suggesting a defect in BMP ligand bioavailability mediates the CFP1-deficient LMP phenotype. Together, these findings define CFP1 as a gatekeeper between the undifferentiated and differentiated state of LMPs during endochondral bone formation and as a physiological regulator of BMP signaling.</div></div><div><h3>Classification</h3><div>Biological Sciences.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 204-215"},"PeriodicalIF":2.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Sperm activation for fertilization requires robust activity of the TAT-5 lipid flippase 精子的受精激活需要TAT-5脂质翻转酶的强大活性。
IF 2.1 3区 生物学
Developmental biology Pub Date : 2025-09-05 DOI: 10.1016/j.ydbio.2025.09.003
Katherine A. Maniates , Saai Suryanarayanan , Alissa Rumin , Morgan Lewin , Andrew Singson , Ann M. Wehman
{"title":"Sperm activation for fertilization requires robust activity of the TAT-5 lipid flippase","authors":"Katherine A. Maniates ,&nbsp;Saai Suryanarayanan ,&nbsp;Alissa Rumin ,&nbsp;Morgan Lewin ,&nbsp;Andrew Singson ,&nbsp;Ann M. Wehman","doi":"10.1016/j.ydbio.2025.09.003","DOIUrl":"10.1016/j.ydbio.2025.09.003","url":null,"abstract":"<div><div>During fertilization, sperm and egg membranes signal and fuse to form a zygote and begin embryonic development. As lipids participate in signaling and membrane fusion, we investigated the role of lipid asymmetry in gametogenesis, fertilization, and embryogenesis. We show that the lipid flippase TAT-5, an essential P4-ATPase that maintains phosphatidylethanolamine asymmetry, is required for both oocyte formation and sperm activation, albeit at different levels of flippase activity. Loss of TAT-5 significantly decreases fertility in both males and hermaphrodites and decreases sperm activation. TAT-5 localizes to the plasma membrane of primary spermatocytes but is sorted away from maturing spermatids after meiosis. We also find that phosphatidylethanolamine asymmetry is lost in residual bodies prior to phosphatidylserine exposure. Our findings demonstrate that phosphatidylethanolamine asymmetry plays key roles during gametogenesis and sperm activation, expanding the roles of lipid dynamics in developmental cell fusion.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 66-78"},"PeriodicalIF":2.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Teaching the complexities of biological sex determination with the goal of creating a more inclusive classroom and perhaps challenging key components of the oversimplified rhetoric of the gender binary 教授生物性别决定的复杂性,目的是创造一个更具包容性的课堂,或许还能挑战性别二元过于简单化的修辞的关键部分。
IF 2.1 3区 生物学
Developmental biology Pub Date : 2025-09-04 DOI: 10.1016/j.ydbio.2025.08.018
Rebecca Delventhal
{"title":"Teaching the complexities of biological sex determination with the goal of creating a more inclusive classroom and perhaps challenging key components of the oversimplified rhetoric of the gender binary","authors":"Rebecca Delventhal","doi":"10.1016/j.ydbio.2025.08.018","DOIUrl":"10.1016/j.ydbio.2025.08.018","url":null,"abstract":"<div><div>Individual belief in a rigid definition of gender underlies significant social costs, from the gender pay gap, violence and discrimination against transgender and gender diverse people, to global economic losses. These beliefs are often rooted in essentialist thinking that gender is distinct, non-overlapping, unchangeable, and biologically based. Gender is a multidimensional social concept, partly informed by perceptions of sex, which is a distinct concept referring to a collection of biological traits. Contrary to the belief that biological sex is strictly binary, the genetic, molecular, and cellular mechanisms that control development of sex-specific tissues and organs can and do result in outcomes that are not strictly male or female. In other words, the mechanisms at play in sex determination suggest that biological sex is not binary, but instead bimodal. To the extent that perceptions of biological sex inform an individual's beliefs about gender, I posit that teaching students about the true complexity of sex determination has the potential to challenge overly simplistic beliefs about <em>gender</em>. If biological sex is neither binary nor immutable, then perhaps gender, a complicated, socially constructed idea, isn't either. Through greater understanding of these developmental processes, students who learn that biological sex is not discrete may have their essentialist beliefs regarding discreteness of gender challenged. They may also gain new evidence to contradict the rhetoric around biological sex that is so prevalent in public discourse, particularly in the justification of anti-transgender legislation. In this article, I briefly review the diversity of sex development mechanisms across the tree of life, with a focus on mammals, and the implications for our understanding of human sex. I discuss some of the contributing factors to our binary beliefs about gender and the negative impacts on different aspects of society. I then review some considerations for gender- and sex-inclusive teaching of developmental biology, including an example lesson plan that I use in my course, along with describing ways in which altering undergraduate students' gender belief systems could potentially reduce gender bias more broadly.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 174-187"},"PeriodicalIF":2.1,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Redundant and novel functions of scube genes during zebrafish development 斑马鱼发育过程中scube基因的冗余和新功能。
IF 2.1 3区 生物学
Developmental biology Pub Date : 2025-09-03 DOI: 10.1016/j.ydbio.2025.09.002
Quoc Duy Tran, Ivana Mirkovic, Lee B. Miles, Joachim Berger, Alasdair J. Wood, Avnika A. Ruparelia, Sara A. Shehni, Peter D. Currie
{"title":"Redundant and novel functions of scube genes during zebrafish development","authors":"Quoc Duy Tran,&nbsp;Ivana Mirkovic,&nbsp;Lee B. Miles,&nbsp;Joachim Berger,&nbsp;Alasdair J. Wood,&nbsp;Avnika A. Ruparelia,&nbsp;Sara A. Shehni,&nbsp;Peter D. Currie","doi":"10.1016/j.ydbio.2025.09.002","DOIUrl":"10.1016/j.ydbio.2025.09.002","url":null,"abstract":"<div><div>The N-glycoprotein SCUBE family (Scube1, Scube2, and Scube3) plays diverse roles in vertebrate development and disease, yet many specific functions of the three family members remain unclear. These proteins exhibit broad tissue expression patterns, exist as soluble or membrane-tethered forms, and can form homo- or heteromeric complexes with each other, exerting both short- and long-range effects. Individual functional characterisation has proved challenging because of overlapping expression patterns and compensatory mechanisms that likely obscure specific roles. To elucidate Scube function, we generated single, double, and triple mutant combinations of the three <em>scube</em> genes in zebrafish and assessed their roles in Hedgehog signalling. Our findings indicate that all three Scube proteins contribute to muscle development at distinct levels, with triple knockout zebrafish larvae displaying near-complete Hedgehog loss-of-function phenotypes. RNA sequencing analysis revealed potential roles for all three <em>scube</em> genes, and specific functions for Scube1 and Scube3 in apoptosis regulation and macrophage biology were identified. Furthermore, the Scube family contains multiple functional domains, and the role of EGF domains in Hedgehog signalling remains contentious. Comparative rescue analysis revealed that full-length <em>scube2</em> mRNA restored slow muscle fibre numbers more efficiently than EGF domain-truncated constructs in <em>scube2</em> knockout zebrafish, demonstrating the importance of EGF domains in Scube2 function. Our results illustrate both redundant and non-redundant functions among Scube family members and provide new insights into the roles of this enigmatic class of developmental regulators.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 79-90"},"PeriodicalIF":2.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Unraveling the developmental heterogeneity of human retinal ganglion cells within the developing retina to study to the continuity of maturation 揭示发育中的视网膜神经节细胞的发育异质性,以研究成熟的连续性。
IF 2.1 3区 生物学
Developmental biology Pub Date : 2025-09-03 DOI: 10.1016/j.ydbio.2025.08.025
Emil Kriukov , Jonathan R. Soucy , Everett Labrecque , Petr Baranov
{"title":"Unraveling the developmental heterogeneity of human retinal ganglion cells within the developing retina to study to the continuity of maturation","authors":"Emil Kriukov ,&nbsp;Jonathan R. Soucy ,&nbsp;Everett Labrecque ,&nbsp;Petr Baranov","doi":"10.1016/j.ydbio.2025.08.025","DOIUrl":"10.1016/j.ydbio.2025.08.025","url":null,"abstract":"<div><div>Tissue development is a complex spatiotemporal process with multiple interdependent components. Anatomical, histological, sequencing, and evolutional strategies can be used to profile and explain tissue development from different perspectives. The introduction of single-cell RNA sequencing (scRNAseq) methods and the computational tools allows to deconvolute developmental heterogeneity and draw a decomposed uniform map. In this manuscript, we decomposed the development of a human retina with a focus on the retinal ganglion cells (RGC). To increase the temporal resolution of retinal cell classes maturation state we assumed the working hypothesis that that maturation of retinal ganglion cells is a continuous, non-discrete process. We have assembled the scRNAseq atlas of human fetal retina from fetal week 8 to week 27 and applied the computational methods to unravel maturation heterogeneity into a uniform maturation track. We align RGC transcriptomes in pseudotime to map RGC developmental fate trajectories against the broader timeline of retinal development. Through this analysis, we identified the continuous maturation track of RGC and described the cell-intrinsic (differentially expressed and variable genes, maturation gene profiles, regulons, transcriptional motifs) and -extrinsic profiles (neurotrophic receptors across maturation, cell-cell interactions) of different RGC maturation states. We described the genes involved in the retina and RGC maturation, including de novo RGC maturation drivers. We demonstrate the application of the human fetal retina atlas as a reference tool, allowing automated annotation and universal embedding of scRNAseq data. Altogether, our findings deepen the current knowledge of the retina and RGC maturation by bringing in the maturation dimension for the cell class vs. state analysis. We show how the pseudotime application contributes to developmental-oriented analyses, allowing to order the cells by their maturation state. This approach not only improves the downstream computational analysis but also provides a true maturation track transcriptomics profile.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 91-104"},"PeriodicalIF":2.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Overexpression of potassium channel Kcna5 alters skeletal patterning in the zebrafish regenerating fin 钾通道Kcna5的过度表达改变了斑马鱼再生鳍的骨骼模式。
IF 2.1 3区 生物学
Developmental biology Pub Date : 2025-09-03 DOI: 10.1016/j.ydbio.2025.09.001
Alexander W. Seaver, Xinxhao Li, M. Kathryn Iovine
{"title":"Overexpression of potassium channel Kcna5 alters skeletal patterning in the zebrafish regenerating fin","authors":"Alexander W. Seaver,&nbsp;Xinxhao Li,&nbsp;M. Kathryn Iovine","doi":"10.1016/j.ydbio.2025.09.001","DOIUrl":"10.1016/j.ydbio.2025.09.001","url":null,"abstract":"<div><div>Skeletal patterning relies on a complex network of molecular and genetic regulators. However, our understanding of pathways governing joint placement and morphogenesis remains incomplete. Prior studies have demonstrated that medially located Cx43 mediated gap junctional intercellular communication (GJIC) inhibits joint formation by the adjacent lateral skeletal precursor cells, and thereby determines skeletal patterning in the teleost regenerating fin. Here, we test the model that Cx43-GJIC regulates joint formation by propagating changes in membrane potential (ΔV<sub>m</sub>). To provide evidence that ΔV<sub>m</sub> is sufficient to influence joint formation, we generated a transgenic line that expresses the <em>X. laevis voltage-gated channel, shaker-related subfamily, member 5</em> (<em>kcna5</em>) behind the temperature-inducible <em>heat shock protein 70</em> (<em>hsp70</em>) promoter. Using this line, we demonstrate that <em>Xl</em>-<em>kcna5</em> overexpression delays <em>evx1</em> expression and causes longer segments. Moreover, the increased segment length in response to Xl-Kcna5 overexpression requires Cx43. These findings support a model whereby potassium channels act together with gap junction channels to influence joint formation, and therefore skeletal patterning, in the zebrafish regenerating fin.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 57-65"},"PeriodicalIF":2.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Rbm8a deficiency causes hematopoietic defects by modulating Wnt/PCP signaling Rbm8a缺乏通过调节Wnt/PCP信号导致造血缺陷。
IF 2.1 3区 生物学
Developmental biology Pub Date : 2025-09-02 DOI: 10.1016/j.ydbio.2025.08.021
Agnese Kocere , Elena Chiavacci , Charlotte Soneson , Seth T. Jacobson , Emma N. Harrison , Kevin Manuel Méndez-Acevedo , Jacalyn S. MacGowan , Harrison H. Wells , Max S. Hiltabidle , Azhwar Raghunath , Jordan A. Shavit , Daniela Panáková , Margot L.K. Williams , Mark D. Robinson , Christian Mosimann , Alexa Burger
{"title":"Rbm8a deficiency causes hematopoietic defects by modulating Wnt/PCP signaling","authors":"Agnese Kocere ,&nbsp;Elena Chiavacci ,&nbsp;Charlotte Soneson ,&nbsp;Seth T. Jacobson ,&nbsp;Emma N. Harrison ,&nbsp;Kevin Manuel Méndez-Acevedo ,&nbsp;Jacalyn S. MacGowan ,&nbsp;Harrison H. Wells ,&nbsp;Max S. Hiltabidle ,&nbsp;Azhwar Raghunath ,&nbsp;Jordan A. Shavit ,&nbsp;Daniela Panáková ,&nbsp;Margot L.K. Williams ,&nbsp;Mark D. Robinson ,&nbsp;Christian Mosimann ,&nbsp;Alexa Burger","doi":"10.1016/j.ydbio.2025.08.021","DOIUrl":"10.1016/j.ydbio.2025.08.021","url":null,"abstract":"<div><div>Thrombocytopenia-Absent Radius (TAR) syndrome is a rare congenital condition with reduced platelets, forelimb anomalies, and variable heart and kidney defects. TAR syndrome is caused by mutations in <em>RBM8A/Y14</em>, a component of the exon junction complex. How perturbing a general mRNA-processing factor causes the selective TAR Syndrome phenotypes remains unknown. Here, we connect zebrafish <em>rbm8a</em> perturbation to early hematopoietic defects via attenuated non-canonical Wnt/Planar Cell Polarity (PCP) signaling. In hypomorphic <em>rbm8a</em> zebrafish, we observe a reduction of <em>cd41</em>-positive thrombocytes. <em>rbm8a</em>-mutant zebrafish accumulate mRNAs with retained introns, including non-canonical Wnt/PCP pathway components resulting in convergent extension defects. We found that reduced <em>rbm8a</em> function interacts with perturbations in non-canonical Wnt/PCP pathway genes w<em>nt5b</em>, <em>wnt11f2</em>, <em>fzd7a</em>, and <em>vangl2</em>, impairing the architecture of the lateral plate mesoderm (LPM) that forms hematopoietic, cardiovascular, kidney, and forelimb skeleton progenitors. Both mutants for <em>rbm8a</em> and for the PCP gene <em>vangl2</em> feature impaired expression of early hematopoietic/endothelial genes <em>runx1</em> and <em>gfi1aa</em>. Together, our data propose aberrant LPM patterning and hematopoietic defects as consequence of attenuated non-canonical Wnt/PCP signaling upon reduced <em>rbm8a</em> function.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 34-56"},"PeriodicalIF":2.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Loss of CMTR1 leads to gastrulation failure and early embryonic lethality CMTR1的缺失导致原肠胚发育失败和早期胚胎死亡
IF 2.1 3区 生物学
Developmental biology Pub Date : 2025-09-01 DOI: 10.1016/j.ydbio.2025.08.022
Janelle M. Welton , Kimberly D. Tremblay , Jesse Mager
{"title":"Loss of CMTR1 leads to gastrulation failure and early embryonic lethality","authors":"Janelle M. Welton ,&nbsp;Kimberly D. Tremblay ,&nbsp;Jesse Mager","doi":"10.1016/j.ydbio.2025.08.022","DOIUrl":"10.1016/j.ydbio.2025.08.022","url":null,"abstract":"<div><div>Cap Methyltransferase 1 (CMTR1) facilitates the addition of a 5’ methyl cap on eukaryotic mRNA molecules. Using a knock-out (KO) allele, we demonstrate that CMTR1plays an essential role during gastrulation. In the absence of CMTR1, mutant embryos undergo early lethality, arresting prior to organogenesis with severe developmental delay apparent at E7.5. Multiple molecular approaches indicate significant disruptions in the ability of the CMTR1-KO embryo to form the three primary germ layers – likely driving the observed gastrulation failure. Our analysis of CMTR1 has revealed an unexpected sexually dimorphic phenotype. Female CMTR1 null embryos are more severely delayed and have increased differentially expressed genes compared to male mutants; presumably causing a variety of downstream consequences and a more severe developmental phenotype. Importantly, we do not observe defects in X-inactivation, suggesting that there are unidentified sexually dimorphic mechanisms active during early embryonic stages, prior to the onset of known differences between XX and XY embryos. In sum, we illustrate the necessity of CMTR1 during embryonic development and reveal novel insights into differences in gene regulation pathways between sexes prior to organogenesis.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 1-12"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144934086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Nuclear hormone receptor regulation of PAL-1/Caudal mediates ventral nerve cord assembly in C. elegans 核激素受体调节PAL-1/尾侧介导线虫腹侧神经束组装
IF 2.1 3区 生物学
Developmental biology Pub Date : 2025-09-01 DOI: 10.1016/j.ydbio.2025.08.023
Nathaniel Noblett , Tony Roenspies , Stephane Flibotte , Antonio Colavita
{"title":"Nuclear hormone receptor regulation of PAL-1/Caudal mediates ventral nerve cord assembly in C. elegans","authors":"Nathaniel Noblett ,&nbsp;Tony Roenspies ,&nbsp;Stephane Flibotte ,&nbsp;Antonio Colavita","doi":"10.1016/j.ydbio.2025.08.023","DOIUrl":"10.1016/j.ydbio.2025.08.023","url":null,"abstract":"<div><div>The regulatory network governed by CDX/<em>Caudal</em> family transcription factors plays critical roles in shaping embryonic neural development. In <em>C. elegans</em>, we found that proper expression of <em>pal-1</em>, the <em>C. elegans Caudal</em> homologue, is required for correct positioning of motor neuron cell bodies in the first larval stage ventral nerve cord (VNC). We identified an upstream regulatory region within the <em>pal-1</em> promoter that drives <em>pal-1</em> expression in a subset of DD and DA neuronal progenitors. We also show that SEX-1, a nuclear hormone receptor, is required for motor neuron positioning in the VNC. Loss of <em>sex-1</em> results in neuronal positioning defects similar to those observed in <em>pal-1</em> mutants. This is in part due to a requirement for SEX-1 in promoting <em>pal-1</em> expression in DD and DA neuronal progenitors during VNC assembly. Double mutant analysis further suggests that <em>sex-1</em> also has <em>pal-1</em>-independent functions. Together, these findings define a transcriptional hierarchy in which the SEX-1 nuclear hormone receptor regulates the tissue-specific activity of PAL-1 to promote proper motor neuron positioning in the VNC and highlight a conserved role for NHR and CDX/Caudal family proteins in central nerve cord formation.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 13-26"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144989802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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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