Janelle M. Welton , Kimberly D. Tremblay , Jesse Mager
{"title":"Loss of CMTR1 leads to gastrulation failure and early embryonic lethality","authors":"Janelle M. Welton , Kimberly D. Tremblay , 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}
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 , Tony Roenspies , Stephane Flibotte , 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}
Izabela Jędrzejowska , Karol Małota , Arnold Garbiec
{"title":"Long-term mitochondria-endoplasmic reticulum complexes in the oocytes and early embryos of a matrotrophic pseudoscorpion Chelifer cancroides","authors":"Izabela Jędrzejowska , Karol Małota , Arnold Garbiec","doi":"10.1016/j.ydbio.2025.08.020","DOIUrl":"10.1016/j.ydbio.2025.08.020","url":null,"abstract":"<div><div>Mitochondria are considered key organelles for proper oocyte growth, maturation, fertilization, and embryo development. During oogenesis, they have been found to be highly dynamic organelles that interact with other cellular components. In this study, we analyzed the morphology and behavior of mitochondria in the oocytes and early embryos of the cosmopolitan pseudoscorpion <em>Chelifer cancroides</em>. Analyses were carried out using light, confocal, and transmission electron microscopy. Our results show that, in the early stages of oocyte growth, mitochondria gather close to the germinal vesicle within an organelle assemblage termed the Balbiani body (Bb). In the Bb, mitochondria increase in number and display a high membrane potential. In advanced previtellogenesis, when the Bb disperses, the mitochondria gradually populate the entire ooplasm and join the endoplasmic reticulum to form mitochondria-endoplasmic reticulum (mt-ER) complexes. Within these complexes, mitochondria significantly change morphology and reduce activity. The mt-ER complexes persist throughout oocyte growth until early embryogenesis. During cleavage, they are unevenly segregated to the micromeres that form the embryo body. Our results suggest that in <em>Chelifer</em>, the Balbiani body plays a role in mitochondrial multiplication. We also discuss the role of the mt-ER complexes and propose that they promote low activity of mitochondria to protect mtDNA and supply the embryo with substantial organelles for the early stages of development.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 318-330"},"PeriodicalIF":2.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925815","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}
Frietson Galis , Alexandra A.E. van der Geer , Tom J.M. Van Dooren , Tamás Szeniczey , Tamás Hajdu , Krisztián Kiss , Ildikó Pap
{"title":"Unusually high prevalence of cervical ribs in an 18th-Century Hungarian town: The impact of a tuberculosis epidemic","authors":"Frietson Galis , Alexandra A.E. van der Geer , Tom J.M. Van Dooren , Tamás Szeniczey , Tamás Hajdu , Krisztián Kiss , Ildikó Pap","doi":"10.1016/j.ydbio.2025.08.019","DOIUrl":"10.1016/j.ydbio.2025.08.019","url":null,"abstract":"<div><div>Tuberculosis (TB) ravaged the Hungarian town of Vác in the 18th century. Nearly all of the young and middle-aged adults buried in the Dominican Church were infected with TB. Therefore, most women were likely infected with <em>Mycobacterium tuberculosis</em> (MTB) during pregnancy. In rodents, disruptions in early gestation, when the head-to-tail patterning of the embryo occurs, often result in an increased incidence of cervical ribs. Because TB severely disrupts pregnancy, we hypothesized that these disruptions would result in an increased number of cervical ribs in Vác residents. We examined 58 skeletons and found, as predicted, that the incidence of cervical ribs is exceptionally high in this population. Cervical ribs are approximately twenty-five times more common than in the healthy general population and shifts of the thoracolumbar boundary two to five times more common. Cervical ribs are usually associated with other congenital anomalies, including other homeotic vertebral transformations. Homeotic transformations at different vertebral boundaries were usually in the same direction and sometimes involved three boundaries. This implies a prolonged disruption of pregnancy and alterations in multiple <em>Hox</em> gene expression domains. Our study emphasizes that a high incidence of cervical ribs indicates vulnerability. Our data support the idea that cervical ribs can be induced not only by genetic changes, but also by infectious diseases and thus by environmental perturbations of pregnancy.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 27-33"},"PeriodicalIF":2.1,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946110","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}
{"title":"Early and transient requirements for FGFR2b/1b ligands in cochlear sensory and neural cell subtype differentiation","authors":"Suzanne L. Mansour, Lisa D. Urness","doi":"10.1016/j.ydbio.2025.08.017","DOIUrl":"10.1016/j.ydbio.2025.08.017","url":null,"abstract":"<div><div>We probed the roles of FGFR2b/1b signaling in mid-gestation cochlear development by inducing dnFGFR2b, a ligand trap that sequesters FGF3 and FGF10. Analyses following E11.5-E18.5 induction showed that FGFR2b/1b ligands are required for normal hair cell numbers, to repress inner hair cell differentiation in the lateral organ of Corti and to promote outer hair cell differentiation. FGFR2b/1b ligands also repress outer support cell numbers and promote differentiation of outer pillar cells and Deiters' cells. Finally, these ligands also promote normal cochlear ganglion size and morphology as well as differentiation of CALB2-positive spiral ganglion neuronal subtypes. Delaying the start of dnFGFR2b expression to successive days after E11.5 revealed a critical period of E11.5-E13.5 for FGFR2b/1b signaling in sensory development and of E11.5-E14.5 in ganglion development. Strikingly, even transient induction of dnFGFR2b from E11.5-E12.5 was sufficient to largely recapitulate the phenotypes seen following long-term induction, suggesting that some of the key FGFR2b/1b ligand-dependent events controlling cochlear cell subtype differentiation occur long before such differentiation is evident, and suggesting a new window within which to search for regulators of cochlear differentiation.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 331-347"},"PeriodicalIF":2.1,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946160","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}
{"title":"Multilineage potential induced by reconstruction of three-dimensional structures in mouse fetal brain cells","authors":"Ken Ohnishi , Jun-ichi Sagara , Tomoya Fujita","doi":"10.1016/j.ydbio.2025.08.015","DOIUrl":"10.1016/j.ydbio.2025.08.015","url":null,"abstract":"<div><div>We examined whether the multilineage potential of mouse fetal brain cells is induced by the three-dimensional (3D) structural reconstruction. Dissociated single cells from the cerebral hemispheres of mouse fetuses at embryonic day 14.5–15 (E14.5–15) rapidly aggregated into cell clusters, forming spherical cell aggregates (SCAs). Immunofluorescence staining revealed that SCAs were positive for Map2 but negative for Nestin, GFAP, and markers of undifferentiated cells such as Oct4, SSEA-1, ALDH2, and CD133. During culture of SCAs in embryonic stem cell medium, SCAs subsequently developed into embryoid bodies (EBs), which began to exhibit positive immunofluorescence staining for Oct4. Reverse transcription–polymerase chain reaction (RT-PCR) and Western blotting analyses further confirmed the expression of Oct4 and Nanog at the gene and protein levels. Differentiated cells of EBs induced by culture in various types of media showed positive immunofluorescence staining for lineage-specific markers, including AFP, α-SMA, GFAP, Map2 and C-peptide and expressed the corresponding genes and proteins. These results suggest that mouse fetal brain cells can regain multilineage potential through the reconstruction of 3D structures without genetic modification. Our findings indicate that 3D culture systems may support non-genetic reprogramming strategies in regenerative medicine by activating intrinsic plasticity of cells.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 348-359"},"PeriodicalIF":2.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946124","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}
Mingfu Xiong , Yun Chen , Shilong Wang , Zhaobo Zhang , Danyang Fan , Jiaying Li , Xia He , Yongsheng Zhang , Yilong Yao
{"title":"Liquid–liquid phase separation (LLPS) in skeletal muscle: A new frontier in muscle biology","authors":"Mingfu Xiong , Yun Chen , Shilong Wang , Zhaobo Zhang , Danyang Fan , Jiaying Li , Xia He , Yongsheng Zhang , Yilong Yao","doi":"10.1016/j.ydbio.2025.08.016","DOIUrl":"10.1016/j.ydbio.2025.08.016","url":null,"abstract":"<div><div>Liquid–liquid phase separation (LLPS) is a crucial biophysical process that enables dynamic compartmentalization within cells, gaining prominence in recent research on cellular organization. However, its implications for skeletal muscle—a vital tissue for movement and metabolic regulation—remain largely uncharted. This review highlights recent insights into LLPS's roles in other tissues while examining its potential functions in skeletal muscle development, regeneration, and disease. By synthesizing existing knowledge, we propose that exploring LLPS in skeletal muscle could uncover fundamental aspects of muscle physiology and offer innovative therapeutic avenues for muscle-related disorders. A deeper grasp of LLPS may thus transform our understanding and treatment of skeletal muscle pathologies.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 308-317"},"PeriodicalIF":2.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916561","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}
{"title":"Germ cell formation and reproduction in tunicates","authors":"Yasunori Sasakura , Takeshi Sunanaga , Takeshi A. Onuma , Honoo Satake","doi":"10.1016/j.ydbio.2025.08.013","DOIUrl":"10.1016/j.ydbio.2025.08.013","url":null,"abstract":"<div><div>Because tunicates are the closest living relatives of vertebrates within the phylum Chordata, understanding the mechanisms of tunicate germ cell formation is essential to infer this process in ancestral chordates. Vasa-localization to primordial germ cells (PGCs), PGC formation biased to the posterior side of embryos, and transcriptional silencing by phosphorylation of RNA polymerase II are the core PGC-forming events inherited from the shared ancestor of protostomes and deuterostomes. Neuropeptide- and peptidase-mediated regulations of oocyte maturation are examples of mechanisms observed in both vertebrates and tunicates. However, the pathways that activate and regulate these mechanisms, such as the hypothalamus–pituitary–gonad axis, are not always conserved between tunicates and vertebrates, suggesting that these animals achieved the same end-products via different molecular mechanisms. Tunicates are divided into the classes Ascidiacea, Thaliacea, and Larvacea, each of which exhibits specific characteristics in germ cell formation. Some ascidians form colonies of interconnected zooids, each having regenerative capacity sufficient to regrow the entire body, including gametes, from a tiny body piece. Larvaceans maintain their tadpole shape throughout their very short life cycle: they manage to complete their gamete formation using small gene sets encoded in the shortest genomes yet observed among non-parasitic animals. These group-specific characteristics are likely to reflect different strategies for ensuring survival in the respective environments.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 226-249"},"PeriodicalIF":2.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144880286","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}
Ivano Mocavini , Anna Mallol , Arantxa Gutierrez , Paul Chammas , Ana Carretero , André Dias , Enrique Blanco , Irene Rodriguez Arce , Moises Mallo , Luciano Di Croce , Bernhard Payer
{"title":"The PRC2-associated factor EPOP is required for Hox gene regulation during axial development in mice","authors":"Ivano Mocavini , Anna Mallol , Arantxa Gutierrez , Paul Chammas , Ana Carretero , André Dias , Enrique Blanco , Irene Rodriguez Arce , Moises Mallo , Luciano Di Croce , Bernhard Payer","doi":"10.1016/j.ydbio.2025.08.014","DOIUrl":"10.1016/j.ydbio.2025.08.014","url":null,"abstract":"<div><div>The Polycomb repressive complex 2 (PRC2) is an essential modulator of gene repression. We previously reported that, in mouse embryonic stem cells, PRC2 associates with elonginB/C through EPOP, which allows for low-level expression of target genes. Here we investigate the role of EPOP <em>in vivo</em> by generating a mouse knockout (KO) model. We show that <em>Epop</em> KO mice are viable and fertile but display highly penetrant posterior homeotic transformations of the axial skeleton, which can be partially recapitulated by deletion of only the maternal allele. <em>Epop</em>-depleted embryos present a shift of the anterior boundary of expression of certain <em>Hox</em> genes. Tissue-specific RNA sequencing of embryos suggests that the <em>Hox</em> activation defect originates at the level of the presomitic mesoderm. Overall, we find that EPOP prevents premature activation of a subset of <em>Hox</em> genes, and that this is required for correct body patterning along the antero-posterior axis.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 250-259"},"PeriodicalIF":2.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144885487","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}