Developmental biology最新文献

{"title":"Towards functional genetics in the European amphioxus: Efficient CRISPR/Cas9 editing reveals Ascl1/2.1 requirement for peripheral nervous system development","authors":"Rafath Chowdhury ,&nbsp;Agnès Roure,&nbsp;Sébastien Darras","doi":"10.1016/j.ydbio.2025.08.012","DOIUrl":"10.1016/j.ydbio.2025.08.012","url":null,"abstract":"<div><div>Amphioxus, or cephalochordates, have a key phylogenetic position among chordates and serve as pivotal invertebrate models for investigating the evolutionary origins of vertebrate traits. Although functional genetic tools have recently been developed, their application has been limited to the Floridian and Asian species, <em>Branchiostoma floridae</em> and <em>Branchiostoma belcheri</em>, respectively. In this study, we established a CRISPR/Cas9-based genome editing protocol to generate F0 mosaic mutants (crispants) in the European amphioxus <em>B. lanceolatum</em>. As a proof of concept, we targeted the <em>Bl-Ascl1/2.1</em> gene, a putative regulator of epidermal sensory neuron (ESN) development in the peripheral nervous system coding for a bHLH transcription factor. Using a novel microinjection method of the sgRNA/Cas9 complex in fertilized eggs and two-cell stage embryos, we demonstrated the disruption of <em>Bl-Ascl1/2.</em>1 that resulted in a partial to complete loss of ESNs. Importantly, this phenotype could be rescued by <em>Bl-Ascl1/2.</em>1 mRNA microinjection. These findings demonstrate the efficiency of CRISPR/Cas9-mediated gene editing in <em>B. lanceolatum</em> and establish a foundation for future functional studies in this emerging EvoDevo model.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 218-225"},"PeriodicalIF":2.1,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144867049","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":"Outside Back Cover - Graphical abstract TOC/TOC in double column/Cover image legend if applicable, Bar code, Abstracting and Indexing information","authors":"","doi":"10.1016/S0012-1606(25)00220-9","DOIUrl":"10.1016/S0012-1606(25)00220-9","url":null,"abstract":"","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"526 ","pages":"Page OBC"},"PeriodicalIF":2.1,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840954","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":"A modular enhancer mediates SCRT2 repression of ISLET1 in the spinal cord","authors":"Vitória S. Botezelli ,&nbsp;Tatiane Y. Kanno ,&nbsp;Ee Shan Liau ,&nbsp;Carolina P. Goes ,&nbsp;Shirley de La Cruz Anticona ,&nbsp;Ana Paula Azambuja ,&nbsp;Marcos Simoes-Costa ,&nbsp;C.Y. Irene Yan","doi":"10.1016/j.ydbio.2025.08.008","DOIUrl":"10.1016/j.ydbio.2025.08.008","url":null,"abstract":"<div><div>How transcriptional programs coordinate the transition from neural progenitors to lineage-committed neurons in the spinal cord remains poorly understood. While much is known about transcription factors acting in the proliferative and differentiated zones, the role of intermediate zone (IZ) factors during lineage specification is less clear. Here, we investigate the function of <em>SCRATCH2</em> (<em>SCRT2</em>), expressed in the postmitotic cells of the IZ, during dorsal interneuron differentiation. Overexpression of SCRT2 in vivo reduced the number of ISLET1+ dorsal interneurons. Chromatin profiling revealed that SCRT2 primarily binds to intergenic, transcriptionally inactive regions near neurogenic genes. Among these, we identified a conserved regulatory element, <em>ECR4</em>, located between <em>ISLET1</em> and <em>PARP8</em>. Functional assays showed that <em>ECR4</em> drives neural transcription and is composed of two subregions: <em>ECR4B</em>, an enhancer activated by ISLET1 and POU4F1, and <em>ECR4A</em>, which contains SCRT2 binding motifs and mediates transcriptional repression. Mutation of the vCES-box, a predicted SCRT2-binding motif within <em>ECR4A</em>, abolished repression, confirming a repressive regulatory interaction. Together, these data support a model in which SCRT2 represses ISLET1 through <em>ECR4</em> to modulate dI3 lineage specification. These findings identify a novel regulatory mechanism linking intermediate zone transcriptional repression to dorsal interneuron development in the spinal cord.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 297-307"},"PeriodicalIF":2.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862206","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":"HOXA5-driven transcriptional program in lung development","authors":"Béatrice Frenette ,&nbsp;Josselin Guéno ,&nbsp;Nicolas Houde ,&nbsp;Jennifer H. Mansfield ,&nbsp;Lucie Jeannotte","doi":"10.1016/j.ydbio.2025.08.010","DOIUrl":"10.1016/j.ydbio.2025.08.010","url":null,"abstract":"<div><div>Despite the fundamental role of <em>Hoxa5</em> in mouse development revealed by the well-characterized phenotypes of <em>Hoxa5</em> mutant mice, HOXA5-dependent regulatory networks remain ill-defined. We generated a <em>Hoxa5</em>^FLAG epitope-tagged mouse line to perform ChIP-seq experiments and uncover genome-wide occupancy of the HOXA5 protein. This was done in the developing lung tissue, in which <em>Hoxa5</em> plays a predominant role since <em>Hoxa5</em>^-/- mouse mutants die at birth from respiratory defects. ChIP-seq allowed us to define an <em>in vivo</em> HOXA5 binding motif and its widespread genome distribution in the embryonic lung. Combined with ATAC-seq assays and epigenetic analyses, HOXA5 targets were identified. They include <em>Hox</em> genes known to show expression changes in lungs from <em>Hoxa5</em> null mutant embryos. Moreover, several key actors of lung morphogenesis were found to possess HOXA5-binding sites and appeared as potential targets of HOXA5. Impact of the loss of <em>Hoxa5</em> function on their expression was confirmed by <em>in situ</em> hybridization. These targets include members of the FGF10, SHH, BMP4 and WNT2 signaling pathways. Altogether, these data unveil the crucial role of HOXA5 in the coordinated control of the signaling networks instructing lung development.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 191-205"},"PeriodicalIF":2.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858975","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":"Mitosis Localization Signal (MLS) extends KA1 and regulates MELK kinase localization to plasma membrane and activity in Xenopus embryo","authors":"Caroline Badouel ,&nbsp;Guillaume Hatte ,&nbsp;Claude Prigent ,&nbsp;Jacek Z. Kubiak ,&nbsp;Jean-Pierre Tassan","doi":"10.1016/j.ydbio.2025.08.011","DOIUrl":"10.1016/j.ydbio.2025.08.011","url":null,"abstract":"<div><div>MELK is a cell-cycle dependent serine/threonine protein kinase whose expression is elevated in proliferating and cancer cells. In the <em>Xenopus</em> embryo, MELK overexpression induces cytokinesis failure, leading to multinucleated cells. This phenotype requires MELK catalytic activity, which correlates with MELK conformational modification and its localization to the cell membrane. How MELK activation and localization are coordinated remains unclear. Here, we show that in Xenopus gastrula epithelial cells MELK is abruptly enriched at the plasma membrane starting precisely from the metaphase-to-anaphase transition until early interphase. We show that deletion of the Kinase-Associated domain 1 (KA1), involved in binding to anionic phospholipids, does not abolish MELK localization to the plasma membrane. By a series of deletions, we identified a new 41-amino-acid domain, called Mitosis Localization Signal (MLS) that regulates MELK localization to the plasma membrane in dividing cells. We show that MLS cooperates with KA1 to regulate MELK localization and is necessary to induce cytokinesis failure when MELK is overexpressed. Our findings highlight the importance of MLS in MELK localization and in regulating MELK activity.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 206-217"},"PeriodicalIF":2.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858976","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":"Nkx2.5 triggers vascular remodeling in chicken but not in emu wing mesoderm","authors":"Ingrid Rosenburg Cordeiro ,&nbsp;Satomi F. Ono ,&nbsp;Aoi Shinkai ,&nbsp;Hinako Iwashige ,&nbsp;Reiko Yu ,&nbsp;Guojun Sheng ,&nbsp;Mikiko Tanaka","doi":"10.1016/j.ydbio.2025.08.007","DOIUrl":"10.1016/j.ydbio.2025.08.007","url":null,"abstract":"<div><div><em>Nkx2.5</em> is a key NK-2 homeobox transcription factor with well-established roles in cardiogenesis and the development of other splanchnopleure-derived structures in vertebrates. Unexpectedly, <em>Nkx2.5</em> is also expressed in the developing wings of emus, a flightless birds with vestigial wings, and its misexpression in chicken wing fields was reported to cause limb reduction. To further investigate the cellular effects of Nkx2.5 in the limb field, we overexpressed <em>Nkx2.5</em> in the somatic layer of the lateral plate mesoderm at the wing level of chicken embryos via localized electroporation. This induced ectopic expression of the hemangiogenic gene <em>Scl,</em> accompanied by disorganization of the somatopleure and changes in the ventral vasculature, suggesting a transient activation of hemangioblast-like programs in this tissue. In contrast, analysis of single-cell RNA sequencing datasets from emu embryos revealed that <em>Nkx2.5</em>-positive cells were predominantly found within the muscle clusters, including a subset of co-expressing lateral mesoderm markers such as <em>Hand2</em> and <em>Prrx1</em>. However, these cells did not show a hemangiogenic transcriptional profile, and expression of <em>Scl</em> was not detected. These findings suggest that although localized <em>Nkx2.5</em> expression can promote vascular changes under experimental conditions in chicken, it does not induce comparable effects during normal emu limb development. Our results underscore the context-dependent effect of <em>Nkx2.5</em>, which reflect the broader transcriptional environment and lineage history of the cells in which it is expressed. This study helps refine our understanding of <em>Nkx2.5</em> function in limb mesoderm and provide further insights into the unique developmental trajectory of emu wing formation.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 182-190"},"PeriodicalIF":2.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854873","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":"Elongation of the nascent avian foregut requires coordination of intrinsic and extrinsic cell behaviors","authors":"Olivia Powell,&nbsp;Emily Garcia,&nbsp;Vanshika Sriram,&nbsp;Yi Qu,&nbsp;Nandan L. Nerurkar","doi":"10.1016/j.ydbio.2025.08.009","DOIUrl":"10.1016/j.ydbio.2025.08.009","url":null,"abstract":"<div><div>The foregut tube gives rise to the lungs and upper gastrointestinal tract, enabling vital functions of respiration and digestion. How the foregut tube forms during embryonic development has historically received considerable attention, but over the past few decades this question has primarily been addressed indirectly through studies on morphogenesis of the primitive heart tube, a closely related process. As a result, many aspects of foregut development remain unresolved. Here, we exploit the accessibility of the chick embryo to study the initial formation of the foregut tube, combining embryology with fate mapping, live imaging, and biomechanical analyses. The present study reveals that the foregut forms and elongates over a narrower time window than previously thought, and displays marked dorso-ventral and left-right asymmetries early in its development. Through tissue-specific ablation of endoderm along the anterior intestinal portal, we confirm its central role in driving foregut morphogenesis, despite not directly contributing cells to the elongating tube. We further confirm the important role of this cell population in formation of the heart tube, with evidence that this role extends to later stages of cardiac looping as well. Together, these data reveal the need for an intricate balance between intrinsic cell behaviors and extrinsic cues for normal foregut elongation, and set the stage for future studies aimed at understanding the underlying molecular cues that coordinate this balance.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 277-288"},"PeriodicalIF":2.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854872","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":"G2 regulatory processes require speedbump for Wee1 kinase activity","authors":"Rachel M. Warga,&nbsp;Donald A. Kane","doi":"10.1016/j.ydbio.2025.08.006","DOIUrl":"10.1016/j.ydbio.2025.08.006","url":null,"abstract":"<div><div>Wee1 is a conserved Cdk1 inhibitory kinase operating at the G2/M checkpoint to prevent entry into mitosis until the genome has been surveilled and replication is complete. We report here that the early arrest mutant <em>speedbump</em> is a loss-of-function mutation in the zebrafish ortholog of <em>wee1</em>. Like other creatures lacking Wee1 kinase, cells in the mutant enter mitosis early. Eventually, mutant cells exhibit chromosomal defects and undergo apoptosis. Live recordings of the mutant reveal that as gastrula cells transition from maternal to zygotic control, their cell cycle gets progressively shorter rather than lengthening as seen in wild-type embryos. This suggests that Wee1 kinase inhibition is part of a mechanism to slow the cell cycle that we posit is independent of its role in blocking entry into mitosis to prevent DNA damage. Supporting this view, we show that Wee1 kinase is also crucial for tissues that normally exit the cell cycle in the G2 phase. In the absence of Wee1 kinase, hatching gland cells, which typically cease dividing before <em>speedbump</em> defects appear, no longer remain in G2, and instead advance into mitosis before prematurely dying. Finally, we demonstrate that Wee1 kinase is essential for the endoreplication cycle in the yolk cell. We show that wild-type yolk cell nuclei transition to an S and G endocycle after they cease mitosis in the blastula. However, without Wee1 kinase these nuclei have difficulty attaining this endocycle and sometimes regress back into mitosis. We conclude that besides the regulation of mitotic timing, Wee1 kinase has other G2 regulatory roles not previously reported in which controlling entry into mitosis must be coordinated with other cellular processes.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 165-181"},"PeriodicalIF":2.1,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820826","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":"Building bridges for oocyte growth: regulation of C. elegans germline architecture and function by oriented cell divisions","authors":"Réda M. Zellag ,&nbsp;Kimia Zarnani ,&nbsp;Abigail R. Gerhold ,&nbsp;Jean-Claude Labbé","doi":"10.1016/j.ydbio.2025.08.005","DOIUrl":"10.1016/j.ydbio.2025.08.005","url":null,"abstract":"<div><div>In most animals, the growth of oocytes depends on the delivery of cytoplasm from other germ cells (“nurse” cells) via cytoplasmic bridges. In some cases, such as in mice and Drosophila, these bridges are formed via incomplete cytokinesis and connect the germ cells to the oocyte directly. In other animals, like the nematode <em>Caenorhabditis elegans</em> (<em>C. elegans</em>), germ cells are connected to an anucleate core of cytoplasm, termed the rachis, that supplies materials to the oocyte. This difference in germline architecture poses an interesting challenge for tissue development. Whereas in the first case, stabilization of the cytokinetic ring between dividing germ cells produces the final organization, with the total number of cytoplasmic bridges being one fewer than the total number of germ cells; in the second scenario, germ cell division must produce two daughter cells each with their own connection to the rachis, with the total number of cytoplasmic bridges being equal to the number of germ cells. The cellular and molecular mechanisms that enable germ cells to form and maintain this latter type of architecture are incompletely understood but have been under increasing scrutiny over the last years. Here we review the recent progress in understanding <em>C. elegans</em> germline development from a tissue architecture perspective.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 91-96"},"PeriodicalIF":2.1,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815972","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":"POGLUT2/3 mediated EGF O-glucosylation promotes separation of digits 2 and 3 by influencing fibrillin network reorganization, signaling, and cell dynamics","authors":"Sanjiv Neupane ,&nbsp;Isabella A. Janowicz ,&nbsp;Alan R.F. Godwin ,&nbsp;Kaitlyn E. Donnelly ,&nbsp;Richard C. Grady ,&nbsp;Robert S. Haltiwanger ,&nbsp;Clair Baldock ,&nbsp;Bernadette C. Holdener","doi":"10.1016/j.ydbio.2025.08.004","DOIUrl":"10.1016/j.ydbio.2025.08.004","url":null,"abstract":"<div><div>The separation of individual digits is dependent on establishment of digit-interdigit periodicity, remodeling of the interdigital mesenchyme, and invagination of interdigital epithelial tongues. In Protein <em>O</em>-glucosyltransferase 2 and 3 double knockout (<em>Poglut2/3 DKO</em>) mice, digits 2 and 3 are fused, suggesting a defect in one or more processes. POGLUT2/3 add <em>O</em>-linked glucose to epidermal growth factor-like (EGF) repeats. Syndactyly is also observed when genes encoding the POGLUT2/3 substrates fibrillin 2 (FBN2) or both Nidogen 1 and 2 (NID1/2) are knocked out, suggesting that <em>O</em>-glucosylation is important for their function or localization. In this study, we evaluated the distribution of these substrates during digit separation and the effects of the <em>Poglut2/3 DKO</em> on their localization and cell behavior. During digit separation, the FBNs underwent a dramatic reorganization. Aberrant levels and distribution of the FBNs were observed in the <em>Poglut2/3 DKO</em> and microfibrils isolated from <em>Poglut2/3 DKO</em> skin showed altered periodicity in Fibrillin microfibrils. In contrast, the <em>Poglut2/3 DKO</em> had no effect on the levels or localization of NID1. In <em>Poglut2</em>/3 <em>DKOs</em>, bone morphogenetic protein (BMP) signaling was reduced during digit development, especially in the anterior autopod. Early anterior reduction of BMP signaling could potentially affect spacing of digits 2 &amp; 3. While later reduction of BMP signaling in the <em>Poglut2/3 DKO</em> in the digit 2–3 region was likely responsible for defects in clearance of interdigital mesenchyme and interdigital tongue morphogenesis. These results highlight the importance of POGLUT2/3 mediated <em>O</em>-glucosylation for FBN microfibril organization and raise the possibility that <em>O</em>-glucose modulates the biological or physical properties of the FBN microfibril network.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Pages 147-164"},"PeriodicalIF":2.1,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815973","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}