Developmental biology最新文献

{"title":"Genetic knockout suggests Isl1 enhancer redundancy in mouse hindlimb development","authors":"Seth Olson ,&nbsp;Hiroko Kawakami ,&nbsp;Alexandra Maria Nichitean ,&nbsp;Corinne Boerner ,&nbsp;Amel Awad ,&nbsp;Dylan Corcoran ,&nbsp;Cailin McMahon ,&nbsp;Ryuichi Nishinakamura ,&nbsp;Maureen Cetera ,&nbsp;Yasuhiko Kawakami","doi":"10.1016/j.ydbio.2025.09.014","DOIUrl":"10.1016/j.ydbio.2025.09.014","url":null,"abstract":"<div><div><em>Isl1</em> encodes a LIM homeodomain transcription factor, which is expressed in hindlimb progenitor cells in the lateral plate mesoderm and is required for initiating hindlimb development. Previous studies by lacZ transgenesis in mouse embryos identified a cis-element located 3’ to the <em>Isl1</em> gene, which could drive lacZ reporter expression in hindlimb progenitor cells and the branchial arch ectoderm. We refer to this cis-element as the <em>Isl1</em> hindlimb progenitor enhancer (HLPE). Our previous study also showed that SALL4, a transcription factor, is enriched at the <em>Isl1</em> HLPE, suggesting that SALL4 may regulate <em>Isl1</em> expression through <em>Isl1</em> HLPE. We sought to determine whether <em>Isl1</em> HLPE regulates <em>Isl1</em> expression and created mutant mice that lack the <em>Isl1</em> HLPE sequence by CRISPR/Cas9. The <em>Isl1</em> HLPE^−/− mouse lines, established after breeding with wild-type mice, did not exhibit gross morphological defects, except that their long bones are shorter than those of wild type. The shorter long bone phenotype was observed in the mid-gestation stage and was associated with misregulation of the expression of several chondrogenic genes, suggesting that the deletion of HLPE affects chondrogenesis. Although <em>Sall4</em> regulation of <em>Isl1</em> through <em>Isl1</em> HLPE was suspected, skeletal analysis did not exhibit any synergy between <em>Isl1</em> HLPE^−/− and conditional <em>Sall4</em> mutation. In situ hybridization showed seemingly normal expression of <em>Isl1</em> and its downstream gene <em>Tbx4</em> in <em>Isl1</em> HLPE^−/−, <em>TCre; Sall4</em>^fl/fl mutants, and <em>Isl1</em> HLPE^−/−; <em>TCre; Sall4</em>^fl/fl mutants. Finally, by quantitative gene expression analysis, <em>Isl1</em> expression is reduced but not abolished in <em>Isl1</em> HLPE^−/− and <em>Isl1</em>^+/−; <em>Isl1</em> HLPE ^± embryos, compared to wild-type embryos. Similarly, quantitative imaging analysis after immunostaining showed reduced ISL1 signals in the branchial arch ectoderm in <em>Isl1</em> HLPE^−/− embryos. These results support our notion that the <em>Isl1</em> HLPE sequence functions as an enhancer for <em>Isl1</em> expression in hindlimb progenitor cells and branchial arch ectoderm cells and suggest that multiple redundant enhancers co-regulate <em>Isl1</em> expression.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 217-227"},"PeriodicalIF":2.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091246","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":"Reorganization of H3K9me2-modified chromatin regions during mouse embryonic development","authors":"Diana Fulmer ,&nbsp;Emily J. Shields ,&nbsp;Andrey Poleshko ,&nbsp;Jonathan A. Epstein ,&nbsp;Cheryl L. Smith","doi":"10.1016/j.ydbio.2025.09.005","DOIUrl":"10.1016/j.ydbio.2025.09.005","url":null,"abstract":"<div><div>The three-dimensional organization of chromatin in the nucleus is critical in regulating gene expression. There are two classes of large genomic regions demarcated by the repressive chromatin modification histone H3 lysine 9 dimethyl (H3K9me2) and enriched at the nuclear periphery: lamina-associated domains (LADs); and H3K9me2-only domains (KODs) which have minimal lamina contact and are highly enriched for transcriptional enhancers. LADs have been studied in multiple cell types. In contrast, KODs have been characterized only in pluripotent cells and it remains to be determined whether they are fixed or rearrange according to cell type. Analysis of KODs from various embryonic mouse tissues revealed that KODs adopt cell type-specific configurations that correlate with changes in lineage-specific enhancer activity. Within KODs, local cell type-specific depletion of H3K9me2 was enriched for H3K27ac peaks at active lineage-specific enhancers. KODs were also enriched across ultra-long regulatory regions suggesting a role for KODs in long-range gene regulation. These results suggest that KODs are cell-type specific and maintain cell type-specific enhancers in a repressed state to allow for tissue- and stage-specific gene activation.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 188-203"},"PeriodicalIF":2.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091276","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":"Scarecrow, a homolog of mammalian Nkx2.1, regulates the temporal progression and glial differentiation of medulla neuroblasts for the optic lobe development in Drosophila melanogaster","authors":"Cheol-Ho Yun ,&nbsp;Kyungjun Seok ,&nbsp;Gyunghee G. Lee ,&nbsp;Jae H. Park ,&nbsp;Siuk Yoo","doi":"10.1016/j.ydbio.2025.09.012","DOIUrl":"10.1016/j.ydbio.2025.09.012","url":null,"abstract":"<div><div>The <em>Drosophila</em> medulla is the largest structure in the adult visual nervous system. It contains a vast population of interneurons comprising over 80 different cell types generated by medulla neuroblasts (NBs). Aging NBs express a series of temporal transcription factors (tTFs) that contribute to neuronal diversity. Recent studies have shown that an NK-2 homeobox gene <em>scarecrow</em> (<em>scro</em>) works as a tTF covering from middle to late temporal windows; however, how its expression is established over multiple windows and what roles it plays in individual windows remain largely elusive. We found the lack of <em>scro</em> expression in the middle of the Dichaete (D) domain, implying its expression is not in a continuum as previously eluded. Overexpression and knockdown assays of <em>scro</em> or other tTFs using various <em>tTF-Gal4</em> drivers further revealed distinctive roles played by Scro at each window, including the last one. The oldest NBs positive for Tll and Scro found at the most proximal region of the developing medulla field attained expression of Gcm (the master factor of glial differentiation) and Nerfin-1 (a suppressor of dedifferentiation via Notch suppression), which in turn led to NB-to-glia differentiation. Downregulation of either <em>gcm</em> or <em>nerfin-1</em> resulted in the formation of ectopic NBs at the expense of glial cells. Moreover, <em>scro-</em>knockdown led to a loss of Gcm, Nerfin-1, and Prospero expression, misregulation of Notch expression, formation of ectopic NBs, and a substantial reduction in glial cell population, suggesting that Scro acts upstream of Gcm and Nerfin-1. The chromatin-immunoprecipitation (ChIP) assays support that Scro regulates the expression of <em>gcm</em>, <em>nerfin-1</em>, and <em>pros</em>, as well as several tTFs, the expression of which overlaps with Scro. In summary, this study not only verified previously suggested roles of Scro but also uncovered novel features of this gene in various temporal windows, including the promotion of NB-to-glial transition and discontinuous expression within the D domain.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 277-294"},"PeriodicalIF":2.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085417","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":"Intraocular vasculature formation precedes extraocular vasculature penetration of mouse eyes","authors":"Satoshi Imanishi ,&nbsp;Yohei Tomita ,&nbsp;Kazuno Negishi ,&nbsp;Kazuo Tsubota ,&nbsp;Toshihide Kurihara","doi":"10.1016/j.ydbio.2025.09.010","DOIUrl":"10.1016/j.ydbio.2025.09.010","url":null,"abstract":"<div><div>The posterior ocular circulatory system comprises choroidal vasculature and central retinal and posterior ciliary arteries (PCAs) that are fundamental for ocular tissue maintenance. Much is known about the development of the retinal vascular system, but that of the posterior ocular circulation system remain obscure. Therefore, we aimed to clarify the development of the intraocular vasculature involved in the posterior ocular circulation system. Choriocapillaris and hyaloid capillaries are formed <em>in situ</em> and <em>de novo</em> through the endothelial differentiation of hemangioblasts. The intraocular segments of the hyaloid artery penetrate the retina before extraocular segments appear. The intraocular segments of PCAs arise from the hyaloid artery before the extraocular segments reach the eye. The posterior ocular circulation system apparently synchronizes with events throughout the entire process of ocular development. The intraocular vasculature notably formed before the extraocular segments reached the eyes. Our findings provide a novel perspective on ocular development and might facilitate understanding of eye diseases in humans.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 152-162"},"PeriodicalIF":2.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085397","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":"Mouse variants in Taf1c result in reduced survival to birth","authors":"Jennifer L. Watts ,&nbsp;Logan Willeke ,&nbsp;Rolf W. Stottmann","doi":"10.1016/j.ydbio.2025.09.011","DOIUrl":"10.1016/j.ydbio.2025.09.011","url":null,"abstract":"<div><div>Ribosome biogenesis is a key cellular function and disruptions in this process can lead to congenital anomalies or “ribosomopathies” with varying phenotypes including craniofacial malformations and neurodevelopment symptoms. Classically, the mouse is a robust model to understand the molecular mechanisms underlying ribosomopathies to further elucidate human pathogenesis. We identified novel compound heterozygous missense variants in the <em>TATA-box binding protein associated factor, RNA polymerase I subunit C</em> (<em>TAF1C</em>) locus in a patient with some phenotypes consistent with ribosomopathies. <em>TAF1C</em> encodes a subunit of the SL1 complex which is critical for the RNA <em>Pol</em>I complex to initiate ribosomal RNA transcription. We hypothesized that functional <em>TAF1C</em> is required at developmental stages critical for craniofacial and neurodevelopment. To test this hypothesis, we created mouse <em>Taf1c</em> variants orthologous to the human variants using CRISPR-CAS9 technology (<em>Taf1c</em>^{<em>R202Q</em>} and <em>Taf1c</em>^{<em>S428A</em>}). We also created an 11bp deletion to complement the missense variants (<em>Taf1c</em>^{<em>11bpdel</em>}). We created multiple allelic combinations to determine the roles for <em>Taf1c</em> in survival and craniofacial development. Homozygous mice for any of these novel variants were underrepresented at organogenesis stages. We did not observe craniofacial anomalies in any surviving mice. Our results suggest that these specific <em>TAF1C</em> variants are not the cause of any human phenotype present in the patient motivating the study. However, we showed that <em>Taf1c</em> is required for embryonic survival and our studies contribute to knowledge about the role of ribosome biogenesis machinery throughout organogenesis.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 143-151"},"PeriodicalIF":2.1,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069002","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":"Hyperactive PDGFRβ signaling induces cataractogenesis via TGFβ and STAT5-IGF1","authors":"Jesse J. Reardon ,&nbsp;Yixuan Ma ,&nbsp;Nathaniel S. Grabinski ,&nbsp;Yalini Ramamoorthy ,&nbsp;Rebecca L. Packard ,&nbsp;Johnathon G. Schiebel ,&nbsp;Heather L. Chandler ,&nbsp;Gina M. Sizemore","doi":"10.1016/j.ydbio.2025.09.009","DOIUrl":"10.1016/j.ydbio.2025.09.009","url":null,"abstract":"<div><h3>Introduction</h3><div>Cataracts are the world's leading cause of reversible blindness. Although cataract formation is commonly initiated by lens fiber cell defects, cataractogenesis can be characterized by aberrant proliferation and migration of lens epithelial cells. Subsequent overproduction of extracellular matrix components such as fibronectin and collagen by epithelial cells is associated with fibrosis of the lens. Little is known about the role of platelet-derived growth factor receptor β (PDGFRβ) in lens fibrosis. Here, we investigated mice with a conditional knock-in of PDGFRβ hyperactivation using a <em>Fsp1</em>, also known as S100A4, promoter (<em>Fsp1-cre;Pdgfrb</em>^{<em>+/D849V</em>}), which consistently develop cataracts at a young age.</div></div><div><h3>Methods</h3><div>Lenses from <em>Fsp1-cre;Pdgfrb</em>^{<em>+/D849V</em>} mice and age-matched controls were dissected and visualized via microscopy from 9 to 15 weeks. Early transcriptional changes of the lenses were investigated between 10 and 12 day old <em>Fsp1-cre;Pdgfrb</em>^{<em>+/D849V</em>} and control mice via RNA sequencing followed by gene set enrichment analysis. Confirmation of RNA sequencing results and mechanistic investigation of PDGFRβ-induced cataractogenesis were determined in lenses isolated from 15-week-old <em>Fsp1-cre;Pdgfrb</em>^{<em>+/D849V</em>} and control mice.</div></div><div><h3>Results</h3><div>Gross examination of cataractous lenses from <em>Fsp1-cre;Pdgfrb</em>^{<em>+/D849V</em>} mice revealed complete opacification by 15 weeks of age compared to no opacification in age-matched controls. Structural changes in the anterior, equatorial, and posterior lens were observed in histology. RNA sequencing revealed significant enrichment of gene sets related to extracellular matrix deposition and reorganization. Mechanistic investigation revealed major roles for TGFβ, Wnt/β-catenin, SOCS2, and STAT5-IGF1 signaling axes in PDGFRβ-induced cataract formation.</div></div><div><h3>Conclusion</h3><div>PDGFRβ promoted cataractogenesis by modulating pro-fibrotic extracellular matrix changes, likely through TGFβ, Wnt/β-catenin, SOCS2, and the STAT5-IGF1 pathways. Future experiments will delineate the precise role of the STAT5-IGF1 signaling pathway in PDGFRβ-mediated fibrosis and the interplay between PDGFRβ and TGFβ in the lens and whether this signaling is targetable to modulate cataractogenesis.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 228-238"},"PeriodicalIF":2.1,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069297","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":"MicroRNA miR-196a controls neural crest patterning by repressing immature neural ectoderm programs in Xenopus embryos","authors":"Alice M. Godden ,&nbsp;Nicole Ward ,&nbsp;Méghane Sittewelle ,&nbsp;Marco Antonaci ,&nbsp;Rafeeq Mir ,&nbsp;Aleksandr Kotov ,&nbsp;Anne H. Monsoro-Burq ,&nbsp;Grant N. Wheeler","doi":"10.1016/j.ydbio.2025.09.007","DOIUrl":"10.1016/j.ydbio.2025.09.007","url":null,"abstract":"<div><div>Neural crest (NC) cells form a multipotent stem cell population specified during neurulation, which undergo an epithelial-to-mesenchymal transition (EMT) and migrate extensively in the developing embryo, to generate numerous tissues and cell types including the craniofacial skeleton, the peripheral nervous system and pigment cells. The genetic and molecular details of NC specification are governed by a complex, yet still partially understood gene regulatory network (NC-GRN). In particular, the precise function of microRNAs (miRNA) in this network remains poorly characterized. MiRNAs are short non-coding 20–22 nucleotides long RNAs, which control gene expression through post-transcriptional repression. Since miRNA-196a is expressed in the developing neural and NC cells of <em>Xenopus laevis</em> embryos, we here investigated miR-196a function in the NC-GRN, by knocking-down its expression using antisense morpholinos. Depletion of miR-196a revealed major NC and craniofacial phenotypes. These defects were preceded by the perturbed expression of key neural, neural border and NC markers such as <em>sox2/3, zic1/3, pax3</em>, <em>sox10</em> and <em>snail2</em>. Using RNA sequencing of individual neural border and NC explants, we have identified a signature of genes up- and down-regulated by miR-196a and validate these with rescue experiments using a miRNA mimic. Our study identifies miR-196a as a key actor of early patterning in the dorsal ectoderm, balancing the extent of immature neural plate progenitors with NC and placode specification, while also promoting neuron differentiation within the neural plate.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 117-127"},"PeriodicalIF":2.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046528","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":"Controllable targeted protein degradation as a promising tool for discovery of novel cellular and developmental mechanisms","authors":"De-Li Shi ,&nbsp;Xuan Zhao ,&nbsp;Chengtian Zhao ,&nbsp;Ming Shao","doi":"10.1016/j.ydbio.2025.09.006","DOIUrl":"10.1016/j.ydbio.2025.09.006","url":null,"abstract":"<div><div>Studying the spatial and temporal roles of essential proteins remains technically challenging. The effectiveness of perturbing gene functions using well established approaches upstream of the protein level, such as conditional knockout and RNA interference or morpholino-mediated knockdown, are often dependent upon the turnover rate of pre-existing proteins. Acute targeted protein degradation technologies can circumvent this limitation, and has emerged as powerful tools for discoveries of previously unrecognized protein functions in highly dynamic cellular and developmental processes. Auxin-inducible degron, degrade green fluorescent protein, degradation tag and proteolysis-targeting chimera are efficient for rapid knockdown of degron-tagged or untagged endogenous proteins in a controllable manner. All these approaches harness the evolutionarily conserved multi-protein E3 ubiquitin ligase complex in targeting proteins for degradation by the proteasome, offering versatile applications for protein functional studies in yeasts, plants, invertebrates, and vertebrates. This review presents the understanding of spatial and temporal protein functions advanced by commonly used auxin-inducible degron, degrade green fluorescent protein and degradation tag technologies. It also mentions the promising therapeutic potentials offered by the proteolysis-targeting chimera. With constant improvements, targeted protein degradation will open up new avenues for unprecedented findings of the dynamic features in a living system.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 163-173"},"PeriodicalIF":2.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052162","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)00259-3","DOIUrl":"10.1016/S0012-1606(25)00259-3","url":null,"abstract":"","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"527 ","pages":"Page OBC"},"PeriodicalIF":2.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026792","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":"Expression and function of new candidate regulators of placodal neurogenesis in Xenopus laevis","authors":"Bertrand Hutlet,&nbsp;Gerhard Schlosser","doi":"10.1016/j.ydbio.2025.08.026","DOIUrl":"10.1016/j.ydbio.2025.08.026","url":null,"abstract":"<div><div>The transcription factor Six1 and its co-activator Eya1 play central and varied roles during the development of sensory neurons derived from the cranial placodes in vertebrates. Previous studies suggested that these proteins promote both the maintenance of proliferative neuronal progenitors and neuronal differentiation. Context-specific interactions of Six1 and/or Eya1 with different cofactors are likely to contribute to the activation of distinct target genes during different stages of placodal neurogenesis. However, while some protein binding partners of Six1 have recently been identified, little is known about Eya1 interaction partners. To uncover additional Eya1 interaction partners with potential roles in placodal neurogenesis, we here conduct a yeast two-hybrid screen in <em>Xenopus laevis</em>. Apart from confirming Six1 (Six1.L) and Six4 (Six4.L and Six4.S) as known protein interaction partners of Eya1, this screen identified 25 additional candidate binding partners including several transcription factors, chromatin modifiers and enzymes involved in posttranslational modifications. Analysis of the expression of genes encoding five of these candidates (<em>garre1, msh6, zmym3, pias4, smarce1</em>) during <em>X. laevis</em> embryogenesis by in situ hybridization, revealed extensive co-expression of each of these with <em>eya1</em> during placodal development. This suggests potential roles of these candidates in the regulation of placodal neurogenesis possibly in conjunction with Eya1. In gain and loss of function studies of the E3 SUMO-ligase Pias4 and the chromatin modifier Smarce1, we confirm essential roles of both of these proteins for placodal neurogenesis but their mode of interaction with Eya1 remains to be further clarified.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 128-142"},"PeriodicalIF":2.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032922","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}