Developmental Dynamics最新文献

{"title":"β-Catenin localization in the ctenophore Mnemiopsis leidyi suggests an ancestral role in cell adhesion and nuclear function.","authors":"Brian M Walters, Lucas J Guttieres, Mayline Goëb, Stanley J Marjenberg, Mark Q Martindale, Athula H Wikramanayake","doi":"10.1002/dvdy.70004","DOIUrl":"https://doi.org/10.1002/dvdy.70004","url":null,"abstract":"<p><strong>Background: </strong>The emergence of multicellularity in animals marks a pivotal evolutionary event, which was likely enabled by molecular innovations in the way cells adhere and communicate with one another. β-Catenin is significant to this transition due to its dual role as both a structural component in the cadherin-catenin complex and as a transcriptional coactivator involved in the Wnt/β-catenin signaling pathway. However, our knowledge of how this protein functions in ctenophores, one of the earliest diverging metazoans, is limited.</p><p><strong>Results: </strong>To study β-catenin function in the ctenophore Mnemiopsis leidyi, we generated affinity-purified polyclonal antibodies targeting Mlβ-catenin. We then used this tool to observe β-catenin protein localization in developing Mnemiopsis embryos. In this article, we provide evidence of consistent β-catenin protein enrichment at cell-cell interfaces in Mnemiopsis embryos. Additionally, we found β-catenin enrichment in some nuclei, particularly restricted to the oral pole around the time of gastrulation. The Mlβ-catenin affinity-purified antibodies now provide us with a powerful reagent to study the ancestral functions of β-catenin in cell adhesion and transcriptional regulation.</p><p><strong>Conclusions: </strong>The localization pattern of embryonic Mlβ-catenin suggests that this protein had an ancestral role in cell adhesion and may have a nuclear function as well.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457231","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":"Active cell proliferation contributes to the enlargement of the nascent nucleus pulposus.","authors":"Rose G Long, Changhee Lee, Clifford J Tabin","doi":"10.1002/dvdy.70005","DOIUrl":"https://doi.org/10.1002/dvdy.70005","url":null,"abstract":"<p><strong>Background: </strong>The notochord is an embryonic organ involved in forming and patterning the spinal column. The mechanism by which the notochord transforms from a continuous rod to a segmented structure excluded from the vertebrae and residing solely as the nucleus pulposus within the intervertebral disc is understudied. The current model of notochordal segmentation suggests that swelling through formation and maturation of the vertebrate cartilage squeezes the notochord cells from the vertebra.</p><p><strong>Results: </strong>Analysis of Collagen 10, a marker for hypertrophic differentiation, as well as evaluation of changes in cell density, reveal that the expansion of the vertebral precursor cells occurs after notochord segmentation has already taken place. We find that the bulk of the nucleus pulposus is derived from accelerated proliferation within the nucleus pulposus itself. In a model of cell proliferation, the increased proliferation at the nucleus pulposus importantly contributes to expand the nucleus pulposus area.</p><p><strong>Conclusions: </strong>Our data is consistent with the hypothesis that notochord cell proliferation contributes to the enlargement of the nucleus pulposus before the vertebra undergo hypertrophy.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457166","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":"Editorial highlights","authors":"Paul A. Trainor","doi":"10.1002/dvdy.773","DOIUrl":"https://doi.org/10.1002/dvdy.773","url":null,"abstract":"&lt;p&gt;Every organism is a model organism for understanding development, evolution, disease, and regeneration, and we have only begun to scratch the surface of the interdisciplinary genetic, molecular, cellular, and developmental mechanisms that regulate these biological processes. These “Highlights” denote exciting advances recently reported in &lt;i&gt;Developmental Dynamics&lt;/i&gt; that illustrate the complex dynamics of developmental biology.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Embryology&lt;/b&gt; “Embryology of the fat-tailed dunnart (&lt;i&gt;Sminthopsis crassicaudata&lt;/i&gt;): A marsupial model for comparative mammalian developmental and evolutionary biology” by Axel Newton, Jennifer Hutchison, Ella Farley, Emily Scicluna, Neil Youngson, Jun Liu, Brandon Menzies, Thomas Hildebrandt, Ben Lawrence, Angus Sutherland, David Potter, Gerard Tarulli, Lynne Selwood, Stephen Frankenberg, Sara Ord, and Andrew Pask. &lt;i&gt;Dev Dyn&lt;/i&gt;. 254.2, pp. 142–157. https://doi.org/10.1002/dvdy.711. Welcome to the fat-tailed dunnart that is making a name for itself as a marsupial model for developmental, evolutionary, and ecological studies. Marsupials currently remain underutilized in developmental biology studies, which limits our understanding of mammalian diversity. Mammals are a highly diverse lineage of vertebrates, comprising nearly 6500 extant species, classified into three clades: Prototheria, Metatheria, and Eutheria, also known as monotreme, marsupial, and placental mammals, respectively. The fat-tailed dunnart is an emerging laboratory animal, and in this study, the authors stablished methods to confirm pregnancy and generate timed embryos. This facilitated the collection and description of dunnart embryo development from cleavage to birth. Furthermore, detailed descriptions of dunnart organogenesis and heterochronic growth patterns, especially in comparisons with other species, highlight the dunnart's accelerated craniofacial and limb development, which are characteristic of marsupials. This makes the dunnart a valuable model system for investigating the molecular and cellular mechanisms’ underlying heterochrony.&lt;/p&gt;&lt;p&gt;In an accompanying study, “Breeding fat-tailed dunnarts (&lt;i&gt;Sminthopsis crassicaudata&lt;/i&gt;) in captivity: revised practices to minimise stress whilst maintaining considerations of wild biology” by Emily Scicluna, Axel Newton, Jennifer Hutchison, Alicia Dimovski, Kerry Fanson, Gail D'Souza, Shiralee Whitehead and Andrew Pask (need to add in doi number and make sure its linked to web), the authors re-examine current captive management techniques for dunnarts, which rely on scent marking for their social communication and interactions. Although dunnarts have been successfully bred in captivity for decades, there are conflicting reports about best practices for the long-term maintenance of this species. The results of this study provide evidence for preferred cage base substrate types and establish and validate methodology for quantifying stress using fecal glucocorticoid metabolite levels as an i","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"254 2","pages":"100-101"},"PeriodicalIF":2.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvdy.773","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breeding fat-tailed dunnarts (Sminthopsis crassicaudata) in captivity: Revised practices to minimize stress whilst maintaining considerations of wild biology","authors":"Emily L. Scicluna,&nbsp;Axel H. Newton,&nbsp;Jennifer C. Hutchison,&nbsp;Alicia M. Dimovski,&nbsp;Kerry V. Fanson,&nbsp;Gail D'Souza,&nbsp;Shiralee Whitehead,&nbsp;Andrew J. Pask","doi":"10.1002/dvdy.755","DOIUrl":"10.1002/dvdy.755","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The fat-tailed dunnart is a small dasyurid marsupial which is emerging as a robust laboratory model for conservation, developmental, and reproductive biology research. While these marsupials present extremely valuable models, housing non-domesticated animals in captivity can present a wide range of potential stressors for the animals, which need to be managed to ensure colony health. Notably, dunnarts rely on scent marking for social communication, which is important to maintain to reduce stress in artificial environments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this study, we examine captive management techniques and provide updated recommendations which consider both scientific and conservation outcomes. Through ongoing management, we observe that recapitulating aspects of a natural environment has a significant impact on stress reduction and improving the overall reproductive fitness of captive-bred colonies. Moreover, our study provides evidence for preferred cage base substrate types, and quantification of stress caused by the cadence of enclosure cleaning using fecal glucocorticoid metabolite levels as an indicator of stress.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study underscores the significance of population management in captive breeding programs, advocating for maintaining genetic diversity and meticulous record-keeping. We have further refined best practice for managing captively bred dunnart colonies, outlining guidelines for enclosure requirements, handling, cleaning, feeding, and lighting during breeding. Overall, the research aims to improve the health and productivity of captive fat-tailed dunnarts, ensuring their continued contribution as a valuable laboratory-based marsupial model and aiding in the conservation of related endangered species, while meeting a balance between maintenance of strict hygiene and alignment with wild-life history.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"254 2","pages":"189-204"},"PeriodicalIF":2.0,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvdy.755","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocytosis mediated by megalin and cubilin is involved in enamel development.","authors":"Aijia Wang, Yangxi Chen, Xinye Zhang, Ming Liu, Shumin Liu, Renata Kozyraki, Zhi Chen","doi":"10.1002/dvdy.771","DOIUrl":"https://doi.org/10.1002/dvdy.771","url":null,"abstract":"<p><strong>Background: </strong>Endocytosis of enamel matrix proteins (EMPs) by ameloblasts is a key process in the mineralization of enamel during the maturation stage of amelogenesis. However, the relevant receptor mediating endocytosis of EMPs is still unclear. The aim of this study was to explore potential endocytic receptors involved in this process.</p><p><strong>Results: </strong>Two endocytic receptors, megalin, and cubilin, were found to be distributed in ameloblasts of mouse incisors and molars during the secretory and maturation stages. Megalin was located at the distal end of ameloblasts during the maturation stage when proteolysis and recycling were the most active. Megalin and cubilin were also expressed in an ameloblast-lineage cell (ALC) line. The immunoelectron microscopy results showed that megalin was positively labeled on the vesicle structures of ALC, where endocytosis happened. Immunofluorescence showed that megalin and cubilin were colocalized with amelogenin, and the absorption of amelogenin was significantly reduced when megalin and cubilin were inhibited by their inhibitor, receptor-associated protein (RAP). Knockdown of megalin and cubilin with siRNA also reduced the ability of ALC to absorb amelogenin.</p><p><strong>Conclusions: </strong>The results of this study suggest that megalin and cubilin are involved in the absorption process of ameloblasts during amelogenesis.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032339","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 novel transgenic reporter of extracellular acidification in zebrafish elucidates skeletal muscle T-tubule pH regulation.","authors":"Leif R Neitzel, Maya Silver, Aaron H Wasserman, Samantha Rea, Charles C Hong, Charles H Williams","doi":"10.1002/dvdy.770","DOIUrl":"https://doi.org/10.1002/dvdy.770","url":null,"abstract":"<p><p>Disruption of extracellular pH and proton-sensing can profoundly impact cellular and protein functions, leading to developmental defects. To visualize changes in extracellular pH in the developing embryo, we generated a zebrafish transgenic line that ubiquitously expresses the ratiometric pH-sensitive fluorescent protein pHluorin2, tethered to the extracellular face of the plasma membrane using a glycosylphosphatidylinositol (GPI) anchor. Monitoring of pHluorin2 with ratiometric fluorescence revealed dynamic and discrete domains of extracellular acidification over the first 72 h of embryonic development. These included acidification of the notochord intercalations, transient acidification of the otic placode, and persistent acidification of the extracellular space of the myotome at distinctly different pH from that within the T-tubules. Knockdown of centronuclear myopathy genes Bin1b (OMIM: 255200) and MTM1 (OMIM: 310400), which disrupt T-tubule formation, also disrupted myotome acidification. In this study we visualize extracellular acidic microdomains in the tissues of whole live animals. This real-time reporter line for directly measuring changes in extracellular pH can be used to illuminate the role of extracellular pH in normal physiological development and disease states.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001683","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":"The cochlea phenotypically differs from the vestibule in the Gfi1^GFP/GFP mouse.","authors":"Zhuo Li, Hongzhi Chen, Hao Feng","doi":"10.1002/dvdy.772","DOIUrl":"https://doi.org/10.1002/dvdy.772","url":null,"abstract":"<p><strong>Background: </strong>Previous studies with Gfi1-mutated lines have shown that Gfi1 is essential for hair cell maturation and survival.</p><p><strong>Results: </strong>We analyzed the phenotype of another Gfi1-mutated line Gfi1^GFP/GFP in the inner ears of neonates at P5-7 and found that the cochlea phenotypically differed from the vestibule in the Gfi1^GFP/GFP mouse. Specifically, there was a marked reduction in hair cells in the cochlea, which was characterized by greater reductions in the outer hair cells but far less reductions (mainly in the basal turn) in the inner hair cells, whereas the vestibular hair cells remained unaffected. These results were consistent with findings from previous studies. Unexpectedly, the number of cochlear non-sensory supporting cells significantly decreased. However, the vestibular supporting cells did not demonstrate any abnormalities in number.</p><p><strong>Conclusion: </strong>Gfi1 exhibits different functions in the cochlea and vestibule during inner ear development.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001691","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":"Editorial highlights","authors":"Paul A. Trainor","doi":"10.1002/dvdy.767","DOIUrl":"10.1002/dvdy.767","url":null,"abstract":"&lt;p&gt;Every organism is a model organism for understanding development, evolution, disease, and regeneration, and we have only begun to scratch the surface of the interdisciplinary genetic, molecular, cellular, and developmental mechanisms that regulate these biological processes. These “Highlights” denote exciting advances recently reported in &lt;i&gt;Developmental Dynamics&lt;/i&gt; that illustrate the complex dynamics of developmental biology.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Cell Differentiation&lt;/b&gt; “Emerging biological functions of Twist1 in cell differentiation” by Mengjie Tu, Bingqian Ge, Jiali Li, Yanbing Pan, Binbin Zhao, Jiayang Han, Jialin Wu, Kaifeng Zhang, Guangchao Liu, Mengwen Hou, Man Yue, Xu Han, Tiantian Sun and Yang An &lt;i&gt;DevDyn&lt;/i&gt; 254.1, pp. 8–25. https://doi.org/10.1002/dvdy.736. Twist1 is a basic helix–loop–helix (bHLH) transcription factor, first identified in Drosophila as a crucial regulator of mesoderm development. Twist1 is evolutionarily highly conserved and can induce epithelial–mesenchymal transition (EMT) during development and in the pathogenesis of cancer metastasis. Twist1, therefore, plays a key role in a variety of developmental processes, including mesoderm formation, neurulation, neural crest cell formation, neurogenesis, and organogenesis. This review article discusses the physiological roles of Twist1 in osteogenic, chondrogenic, and myogenic differentiation and the molecular mechanisms and signaling pathways mediated by Twist1. In addition, it summarizes the structure of Twist1, its post-translational regulation, and roles in developmental disorders and diseases, with a focus on cellular differentiation. Finally, the authors consider Twist1 as a biomarker for mesenchymal stem cells and speculate that stem cell fate can be regulated through metabolic reprogramming as part of a discussion of new strategies for clinical research involving Twist1 as a regulator of EMT and in organogenesis.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Craniofacial Biology&lt;/b&gt; “Transcription factor Meis1b regulates craniofacial morphogenesis in zebrafish” by Viktorie Psutkova, Petr Nickl, Veronika Brezinova, Olga Machonova and Ondrej Machon &lt;i&gt;DevDyn&lt;/i&gt; 254.1, pp. 40–60. https://doi.org/10.1002/dvdy.731. The vertebrate skull is composed of the viscerocranium (splanchnocranium), chondrocranium (neurocranium), and dermatocranium, and the co-ordinated development of tendons, muscles, nerves, cartilage, and bone are necessary for proper jaw formation and functional integration with the skull. MEIS transcription factors (MEIS1, MEIS2, MEIS3) regulate cartilage and bone development during development in mammals such as mice. This study focuses on the key roles of Meis transcription factors in zebrafish craniofacial. Zebrafish have six &lt;i&gt;meis&lt;/i&gt; genes as the zebrafish genome contains two paralogs of each &lt;i&gt;meis&lt;/i&gt; gene due to whole genome duplication in teleosts. The authors generated &lt;i&gt;meis1a&lt;/i&gt;, &lt;i&gt;meis1b&lt;/i&gt;, &lt;i&gt;meis2a&lt;/i&gt;, and &lt;i&gt;meis2b&lt;/i&gt; mutant zebrafish and analyzed their craniofacial skeleto","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"254 1","pages":"6-7"},"PeriodicalIF":2.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvdy.767","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing candidate DLX-regulated genes in the first pharyngeal arch of chick embryos.","authors":"Afshan Sohail, Olivia Nicoll, Andrew J Bendall","doi":"10.1002/dvdy.765","DOIUrl":"https://doi.org/10.1002/dvdy.765","url":null,"abstract":"<p><strong>Background: </strong>Insights into the development and evolution of asymmetrical jaws will require an understanding of the gene regulatory networks that underpin the differential morphogenesis of the maxillary and mandibular domains of the first pharyngeal arch in a variety of gnathostomes. While a robust relationship has been demonstrated between jaw patterning and the Endothelin-Dlx gene axis, much less is known of the next level of genes in the jaw patterning hierarchy.</p><p><strong>Results: </strong>Several genes, whose expression depends on Dlx5 and/or Dlx6, have been identified in mice. Here, we examined the expression patterns of the chick orthologues of some of those genes, namely GSC, PITX1, HAND2, and GBX2, and tested their dependence on endothelin signaling to assess whether there is a conserved regulatory relationship between those genes in the chick embryo. To further validate these genes as direct DLX targets, we identified conserved non-coding sequences containing candidate DLX binding motifs and demonstrated DLX-responsiveness in vitro.</p><p><strong>Conclusions: </strong>The evidence presented in this study combines to support the hypothesis that these four genes are direct targets of DLX transcription factors in the lower jaw-forming tissue.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983052","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":"The link of FOXO1 and FOXO4 transcription factors to development of the lens.","authors":"Rifah N Gheyas, Ruby C Williams, Kelly A Ryan, A Sue Menko","doi":"10.1002/dvdy.766","DOIUrl":"https://doi.org/10.1002/dvdy.766","url":null,"abstract":"<p><strong>Background: </strong>The FOXOs regulate the transcription of many genes, including ones directly linked to pathways required for lens development. However, this transcription factor family has rarely been studied in the context of development, including the development of the lens. FOXO expression, regulation, and function during lens development remained unexplored.</p><p><strong>Results: </strong>In studies of the embryonic lens, we showed that both FOXO1 and FOXO4, which share many downstream targets, are expressed in a differentiation-state-specific manner, most highly in lens epithelial and differentiating cortical fiber cells. Their expression patterns and subcellular distributions suggest both shared and distinct functions. Stabilization of FOXO cytoplasmic pools involved their binding to the chaperone protein 14-3-3. FOXO association with β-catenin linked this transcription complex to fiber cell-specific gene activation. Inhibition of PI3K/Akt signaling promoted FOXO1/FOXO4 nuclear localization in lens epithelial and fiber cells and expression of the CDKi p27 in the lens epithelium where it has been linked to lens cell withdrawal from the cell cycle and initiation of the lens differentiation program. We showed that FOXO1 transcriptional activation is required for the induction of p27 when Akt signaling is blocked, demonstrating the linearity of the PI3K/Akt/FOXO1/p27 pathway.</p><p><strong>Conclusions: </strong>PI3K/Akt signaling regulates FOXO-dependent lens cell differentiation.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964191","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}