Cells and Development最新文献

{"title":"Sall1 regulates microtubule acetylation in mesenchymal cells during mouse urethral development","authors":"Alvin R. Acebedo ,&nbsp;Gen Yamada ,&nbsp;Mellissa C. Alcantara ,&nbsp;Dennis D. Raga ,&nbsp;Tetsuya Sato ,&nbsp;Ryuichi Nishinakamura ,&nbsp;Kentaro Suzuki","doi":"10.1016/j.cdev.2025.204027","DOIUrl":"10.1016/j.cdev.2025.204027","url":null,"abstract":"<div><div>Male embryonic external genitalia (eExG) undergo sexually dimorphic urethral development in response to androgen signaling (urethral masculinization). Whereas androgen is an essential masculinization factor for eExG, the specific molecular and cellular mechanisms are still unclear. <em>Sall1</em> is a transcription factor that has been linked to the congenital disease Townes-Brocks syndrome, which includes anorectal and urogenital malformations. Currently, the functional role of <em>Sall1</em> for normal urethral development is still unclear. In this study, we show that <em>Sall1</em> is required to regulate proper microtubule acetylation to facilitate mesenchymal cell migration during urethral masculinization of mouse eExG. Mutant male mice with loss of function of mesenchymal <em>Sall1</em> exhibited severe urethral defects, without prominent alteration of androgen signaling. Loss of <em>Sall1</em> induced hyperacetylated microtubules in the eExG mesenchyme. Microtubule hyperacetylation resulted in defective fibrillar adhesions and fibronectin expression which impaired cell migration. Our findings reveal a novel mechanism of Sall1-regulated mesenchymal cell migration for urethral development. This mechanism for Sall1 may underlie the etiology of diseases such as Townes-Brocks syndrome.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"182 ","pages":"Article 204027"},"PeriodicalIF":3.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Definition of the characteristic neurogenesis pattern in the neural plate by the Hes1 orthologue gene, her6, during early zebrafish development","authors":"Momo Tsuruoka,&nbsp;Hiroki Tokizaki,&nbsp;Kyo Yamasu","doi":"10.1016/j.cdev.2025.204026","DOIUrl":"10.1016/j.cdev.2025.204026","url":null,"abstract":"<div><div>During vertebrate embryonic development, a distinctive, spotty neurogenesis pattern emerges in the early neural plate, which represents proneural clusters. The determination of this pattern depends on the interaction between proneural genes and bHLH-O-type transcription factor (TF) genes, <em>Hes/her</em>, which suppress neurogenesis. In this study, we focused on the mouse <em>Hes1</em> orthologue, <em>her6</em>, to understand the mechanism that controls neurodevelopmental patterns in the developing brain in zebrafish (<em>Danio rerio</em>). We first assessed the expression pattern of <em>her6</em> in the neural plate, observing that it is consistently expressed in the entire forebrain throughout somitogenesis, including <em>her9</em> expression within it. Meanwhile, the expression patterns of <em>her6</em> changed dynamically in the hindbrain, in contrast to the Notch-independent <em>her</em> genes. The expression pattern was not significantly affected by forced NICD expression and DAPT treatment at the bud stage, showing that <em>her6</em> expression is Notch-independent in the neural plate at this stage. To analyze the roles of <em>her6</em>, we disrupted <em>her6</em> using the CRISPR/Cas9 method. The mutants thus obtained showed a deformed midbrain-hindbrain region and failed to grow to adulthood. At the bud stage, ectopic expression of neurogenesis-related genes was observed in <em>her6</em> mutants in specific regions of the neural plate, where neurogenesis does not occur and which are considered neural progenitor pools (NPPs) in wild-type embryos. Of note, no other Notch-independent <em>her</em> genes are known to be expressed in these NPP regions. In contrast, the expression of regionalization genes in the forebrain and hindbrain was not affected in <em>her6</em> mutants. These findings suggest that <em>her6</em> defines the primary neurogenesis pattern in the neural plate, together with other Notch-independent <em>her</em> genes.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"182 ","pages":"Article 204026"},"PeriodicalIF":3.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The novel role of foxi3 in zebrafish mandibular development","authors":"Xin Chen ,&nbsp;Run Yang ,&nbsp;Tianyu Zhang ,&nbsp;Jing Ma","doi":"10.1016/j.cdev.2025.204016","DOIUrl":"10.1016/j.cdev.2025.204016","url":null,"abstract":"<div><div>Recent studies have identified pathogenic variants in the <em>FOXI3</em> gene associated with craniofacial microsomia pedigrees. In zebrafish, the <em>foxi1</em> gene is considered a functional homolog of the mouse <em>Foxi3</em>. However, research on <em>foxi3a</em> and <em>foxi3b</em>, which display homologous genes in the naming of FOXI3 in zebrafish, has predominantly focused on their roles in epidermal ionocyte function. Our study reveals that disruption of <em>foxi3a</em> or <em>foxi3b</em> results in a reduced number of cranial neural crest cells (CNCCs) and hypoplastic mandibular cartilage in zebrafish. These findings introduce a new perspective on the functional homologs of <em>FOXI3</em> and highlight an unrecognized role of <em>foxi3</em> in zebrafish CNCC and mandibular development.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"182 ","pages":"Article 204016"},"PeriodicalIF":3.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of kidney organoids derived from human expanded potential stem cells","authors":"Zhanpeng Kuang ,&nbsp;Changmiao Pang ,&nbsp;Haiyan Wang ,&nbsp;Xiaocui Wei ,&nbsp;Xianhua Ye ,&nbsp;Xuefei Gao ,&nbsp;Liangzhong Sun","doi":"10.1016/j.cdev.2025.204025","DOIUrl":"10.1016/j.cdev.2025.204025","url":null,"abstract":"<div><div>The establishment of human expanded potential stem cell (hEPSC) presents a unique cellular platform for translational research in kidney organoids. We generated SIX2 reporter and doxycycline (DOX)-inducible YAP overexpression in hEPSC lines using CRISPR-Cas9. Chemical compounds and DOX were added to the culture medium to induce Hippo-YAP signaling, respectively. The hEPSC line containing the SIX2-mCherry reporter gene accurately reflected SIX2 expression in vitro, enabling the real-time tracking of kidney organoid development. A comparative analysis revealed that inhibiting the Hippo-YAP signaling pathway before nephron progenitor cell (NPC) generation effectively increased the number of NPCs, resulting in a more nephron-like structure. However, prolonged inhibition hindered the further maturation of the kidney organoids, leading to differentiation stagnation. Therefore, activating YAP before NPC generation facilitates their maturation, offering effective induction strategies improving kidney organoid differentiation efficiency.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"182 ","pages":"Article 204025"},"PeriodicalIF":3.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular matrix in cardiac morphogenesis, fibrosis, and regeneration","authors":"Ashwini Punde ,&nbsp;Amey Rayrikar ,&nbsp;Shreya Maity,&nbsp;Chinmoy Patra","doi":"10.1016/j.cdev.2025.204023","DOIUrl":"10.1016/j.cdev.2025.204023","url":null,"abstract":"<div><div>The extracellular matrix (ECM) plays a crucial role in providing structural integrity and regulating cell communication essential for organ development, homeostasis, and regeneration, including hearts. Evidence indicates that disruptions in the spatiotemporal expression or alterations in ECM components lead to cardiac malformations, including a wide range of congenital heart diseases (CHDs). Furthermore, research on injured hearts across various vertebrate species, some of which show effective regeneration while others experience irreversible fibrosis, underscores the significance of ECM molecules in cardiac regeneration. This review presents an overview of heart development and the dynamics of ECM during cardiac morphogenesis, beginning with the formation of the contractile heart tube and advancing to the development of distinct chambers separated by valves to facilitate unidirectional blood flow. Furthermore, we discuss research emphasizing the multifaceted roles of secreted molecules in mediating fibrosis and regeneration following myocardial injury.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"182 ","pages":"Article 204023"},"PeriodicalIF":3.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AKAP14 is dispensable for mouse fertility","authors":"Zishuo Xu,&nbsp;Ansar Hussain,&nbsp;Hanwei Jiang,&nbsp;Huan Zhang,&nbsp;Yousaf Raza,&nbsp;Ghulam Mustafa,&nbsp;Jingwei Ye,&nbsp;Botao Yuan,&nbsp;Bo Yang,&nbsp;Qinghua Shi","doi":"10.1016/j.cdev.2025.204032","DOIUrl":"10.1016/j.cdev.2025.204032","url":null,"abstract":"<div><div>A-kinase anchoring proteins (AKAPs) constitute a structurally diverse family of scaffold proteins with significant functional relevance. Various AKAP family members localize to distinct subcellular compartments, such as sperm flagella, via their specific domains. In this study, we investigated the physiological function of AKAP14, a potential functional gene for male fertility due to its high expression in human and mouse testicular tissues. We generated <em>Akap14</em> knockout mice(<em>Akap14</em>^{<em>ins/Y</em>}) using CRISPR/Cas9 technology to assess the role of AKAP14 in male fertility. Our results demonstrate that <em>Akap14</em>^{<em>ins/Y</em>} mice exhibit normal fertility, with a comparable testes-to-body weight ratio, epididymal sperm count, sperm motility, and sperm morphology to wild-type male mice. Furthermore, examination of meiotic prophase I progression revealed a consistent distribution of each substage in <em>Akap14</em>^{<em>ins/Y</em>} testes compared to wild-type testes, indicating that AKAP14 is dispensable for spermatogenesis in mice. In conclusion, despite its high expression level in the testes, AKAP14 depletion does not impact male fertility in mice, suggesting that further in-depth studies of its role in murine spermatogenesis may be unnecessary and could conserve valuable research resources.</div></div><div><h3><strong>In brief</strong></h3><div>AKAP14 is highly expressed in the testes, but our study using <em>Akap14</em> knockout mice reveals that it is dispensable for male fertility and spermatogenesis. Despite its expression in testicular tissues, AKAP14 depletion does not impair sperm function or meiotic progression, suggesting no critical role in murine reproductive health.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"182 ","pages":"Article 204032"},"PeriodicalIF":3.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear localization and transactivation of SYS-1/β-catenin is the result of serial gene duplications and subfunctionalizations","authors":"Arielle K. Wolf,&nbsp;Lori C. Adams-Phillips,&nbsp;Amanda N.D. Adams,&nbsp;Albert J. Erives,&nbsp;Bryan T. Phillips","doi":"10.1016/j.cdev.2025.204013","DOIUrl":"10.1016/j.cdev.2025.204013","url":null,"abstract":"<div><div>β-catenin is a highly conserved multifunctional protein capable of mediating cell adhesion via E-cadherin and transactivation of target genes of the canonical Wnt signaling pathway. The nematode, <em>C. elegans</em> contains four paralogs of β-catenin which are highly specific in their functions. Though similar in overall structure, the four beta-catenins are functionally distinct, each regulating different aspects of development. Of the four, SYS-1 is a key player in Wnt dependent asymmetric cell division (ACD). In ACD, a polarized mother will give rise to a daughter with high nuclear SYS-1 and another with low nuclear SYS-1. Despite sequence dissimilarity, SYS-1 shares a close structural resemblance with human β-catenin where it retains an unstructured amino-terminus (NTD) and 12 armadillo repeats. Using existing genome sequence data from several nematode species, we find that the four β-catenin paralogs result from 3 sequential gene duplications and neofunctionalizations during nematode evolution. SYS-1, however, lacks an unstructured carboxyl-terminus (CTD) that is essential for human β-catenin transactivation processes. This work supports the hypothesis that SYS-1 compensated for the lack of CTD by acquiring novel transactivation domains with cryptic nuclear localization signals in the NTD and the first four armadillo repeats, as shown by transactivation assays in worms and yeast. Furthermore, SYS-1 regulatory domains are not localized to the NTD as in canonical β-catenin and instead spans the entire length of the protein. Truncating SYS-1 abolishes the classical SYS-1 nuclear asymmetry, resulting in daughter cells with symmetrical SYS-1 truncation localization. A screen for SYS-1 physical interactors followed by in vivo SYS-1 localization analyses and effects on cell fate suggest that proper SYS-1 nuclear export is facilitated by XPO-1, while an interaction with IMB-3, an importin β-like protein, suggests import mechanisms. Interestingly, XPO-1 is especially required for lowering SYS-1 in the Wnt-unsignaled nucleus, suggesting a distinct mechanism for regulating asymmetric nuclear SYS-1. In summary, we provide insights on the mechanism of β-catenin evolution within nematodes and inform SYS-1 transactivation and nuclear transport mechanisms.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"182 ","pages":"Article 204013"},"PeriodicalIF":3.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comparative analysis of the chorioallantoic membrane as an experimental model to study angiogenesis and vascular development in the chick and quail embryos","authors":"Domenico Ribatti","doi":"10.1016/j.cdev.2025.204029","DOIUrl":"10.1016/j.cdev.2025.204029","url":null,"abstract":"<div><div>The avian embryo is a model in which experimental embryology and cellular and molecular biology techniques can converge to address fundamental questions of developmental biology. Chick and quail have been powerful partners in the investigation of avian development. Cells from these two species can develop harmoniously in heterospecific combinations, yet each remains histologically distinct, facilitating the fate mapping of transplanted tissues. In this article, we compare the use of the chicken and quail chorioallantoic membrane assay for the study of angiogenic and anti-angiogenic molecules, and of the angiogenic capability of tumor cell lines and tumor biopsy specimens.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"182 ","pages":"Article 204029"},"PeriodicalIF":3.9,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Equine adult, fetal and ESC-tenocytes have differential migratory, proliferative and gene expression responses to factors upregulated in the injured tendon","authors":"Ross E. Beaumont ,&nbsp;Emily J. Smith ,&nbsp;Clara David ,&nbsp;Yasmin Z. Paterson ,&nbsp;Elena Faull ,&nbsp;Deborah J. Guest","doi":"10.1016/j.cdev.2025.204003","DOIUrl":"10.1016/j.cdev.2025.204003","url":null,"abstract":"<div><div>Tendon injuries are a common problem in humans and horses. There is a high re-injury rate in both species due to the poor regeneration of adult tendon and the resulting formation of scar tissue. In contrast, fetal tendon injuries undergo scarless regeneration, but the mechanisms which underpin this are poorly defined. It is also unclear if tendon cells derived from embryonic stem cells (ESCs) would aid tendon regeneration. In this study we determined the responses of adult, fetal and ESC-derived equine tenocytes to a range of cytokines, chemokines and growth factors that are upregulated following a tendon injury using both 2-dimensional (2D) and 3-dimensional (3D) in vitro wound models.</div><div>We demonstrated that in 2D proliferation assays, the responses of fetal and adult tenocytes to the factors tested are more similar to each other than to ESC-tenocytes. However, in 2D migration assays, fetal tenocytes have similarities to both adult and ESC-tenocytes. In 3D wound closure assays the response of fetal tenocytes also appears to be intermediary between adult and ESC-tenocytes. We further demonstrated that while TGFβ3 increases 3D gel contraction and wound healing by adult and fetal tenocytes, FGF2 results in a significant inhibition by adult cells.</div><div>In conclusion, our findings suggest that differential cellular responses to the factors upregulated following a tendon injury may be involved in determining if tendon repair or regeneration subsequently occurs. Understanding the mechanisms behind these responses is required to inform the development of cell-based therapies to improve tendon regeneration.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"181 ","pages":"Article 204003"},"PeriodicalIF":3.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"fos genes in mainly invertebrate model systems: A review of commonalities and some diversities","authors":"Manuel Zúniga-García ,&nbsp;Juan Rafael Riesgo-Escovar","doi":"10.1016/j.cdev.2025.203997","DOIUrl":"10.1016/j.cdev.2025.203997","url":null,"abstract":"<div><div><em>fos</em> genes, transcription factors with a common basic region and leucine zipper domains binding to a consensus DNA sequence (TGA{}TCA), are evolutionarily conserved in eukaryotes. Homologs can be found in many different species from yeast to vertebrates. In yeast, the homologous <em>GCN4</em> gene is required to mediate “emergency” situations like nutrient deprivation and the unfolded protein response. The <em>C. elegans</em> homolog <em>fos-1</em> is required for reproduction and vulval development, as well as in adult homeostasis. In <em>Drosophila melanogaster</em>, there is also a sole <em>fos</em> homolog: the gene <em>kayak</em>, with five isoforms<em>.</em> The <em>kayak</em> locus has been studied in detail. It was originally described as embryonic lethal with a “dorsal open” phenotype. Since then, <em>kayak</em> has been shown to be required for oocyte maturation and as a source for piRNA; for early dorsoventral specification, macrophage function, dorsal closure, endoderm differentiation, and finally during metamorphosis in wing and eye-antennal development. In mammals there are multiple <em>fos</em> loci, each one with alternative splicing giving rise to multiple isoforms. Overall, mammalian <em>fos</em> genes are required for bone, cartilage and tooth formation, and in some instances for placental angiogenesis and retinal function. We review here mainly what is known about <em>fos</em> function in invertebrate model systems, especially during embryogenesis. We propose that <em>fos</em> genes, evolutionarily conserved transcription factors, evolved early during eukaryotic development, and from its inception as part of an environmental stress response machinery, were co-opted several times during development to regulate processes that may require similar cellular responses.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"181 ","pages":"Article 203997"},"PeriodicalIF":3.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}