{"title":"Extracellular matrix in cardiac morphogenesis, fibrosis, and regeneration.","authors":"Ashwini Punde, Amey Rayrikar, Shreya Maity, Chinmoy Patra","doi":"10.1016/j.cdev.2025.204023","DOIUrl":"https://doi.org/10.1016/j.cdev.2025.204023","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"204023"},"PeriodicalIF":2.1,"publicationDate":"2025-03-26","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":"Three-dimensional rosettes in epithelial formation.","authors":"Lila Neahring, Jennifer A Zallen","doi":"10.1016/j.cdev.2025.204022","DOIUrl":"https://doi.org/10.1016/j.cdev.2025.204022","url":null,"abstract":"<p><p>Epithelia are ubiquitous tissues with essential structural, signaling, and barrier functions. How individual cells act collectively to assemble and remodel epithelia throughout development is a fundamental question in developmental biology. Recent studies have revealed that three-dimensional, multicellular rosettes are key intermediates that provide a solution to the challenge of building new epithelia by coordinating local interactions within groups of cells, facilitating the cooperative acquisition of epithelial properties. Rosettes have been observed in nascent epithelia in several species, consisting of groups of cells that assemble cell-cell junctions and apical-basal polarity organized radially around a central lumen. Once formed, rosettes can dynamically expand, move, coalesce, and interact with surrounding tissues to generate a wide range of epithelial structures, including sheets, tubes, cavities, and branched networks. In this review, we describe the cellular and molecular mechanisms that regulate rosette assembly and dynamics and discuss how rosettes serve as versatile intermediates that give rise to a variety of epithelial morphologies. In addition, we present open questions about the mechanisms that initiate and organize rosette behaviors, and we discuss the implications of this collective mode of epithelial formation for understanding embryonic development and human disease.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"204022"},"PeriodicalIF":2.1,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693686","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":"Temporal regulation of endoderm convergence and extension by the BMP activity gradient through mesoderm-dependent and independent mechanisms.","authors":"Chia-Teng Chang, Tony Tsai, Lila Solnica-Krezel","doi":"10.1016/j.cdev.2025.204021","DOIUrl":"10.1016/j.cdev.2025.204021","url":null,"abstract":"<p><p>One hundred years ago, Spemann and Mangold identified the organizer, a critical embryonic region that establishes vertebrate body axes by directing cell fate and morphogenesis. A conserved vertebrate mechanism involves the regulation of a ventral-to-dorsal BMP activity gradient during gastrulation by the organizer-expressed molecules. In zebrafish, BMP signaling controls mesodermal cell convergence and extension (C&E) by inhibiting Planar Cell Polarity (PCP) signaling and regulating cell adhesion. This allows lateral cells to converge toward the dorsal midline while directing ventral cells toward the tail bud. However, BMP's role in endodermal cell movements and the temporal precision of its regulatory functions remain poorly understood. Using optogenetics and other loss- and gain-of-function approaches, we investigated BMP's role in mesoderm and endoderm C&E. We found that low BMP signaling promotes extension in both germ layers, whereas high BMP signaling inhibits their C&E. Remarkably, BMP signaling activation for 1 h rapidly redirected dorsal to ventral migration of both mesodermal and endodermal cells. However, when BMP signaling was selectively elevated in endoderm in embryos with reduced BMP signaling, endoderm still mimicked mesodermal cell movements, indicating that endodermal responses to BMP are non-cell autonomous. We show that movements of endodermal cells in gastrulae with normal or elevated BMP signaling are not entirely dependent on mesoderm or the Cxcl12b/Cxcr4a GPCR pathway, suggesting additional mechanisms underlie endoderm C&E. Our findings highlight the critical role of the BMP morphogen gradient in coordinated C&E movements of mesodermal and endodermal cells. BMP employs both direct and indirect mechanisms to ensure robust embryonic patterning and morphogenesis of germ layers.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"204021"},"PeriodicalIF":2.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639900","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":"Transcending the hegemony of the molecular machine through an organic renewal of biology and biomedicine.","authors":"Amy E Shyer, Alan R Rodrigues","doi":"10.1016/j.cdev.2025.204018","DOIUrl":"10.1016/j.cdev.2025.204018","url":null,"abstract":"<p><p>The dominant approach to the study of living systems in the 20th century into today has been that of a reductionist approach focused on genetics and biochemistry. The hunt for genes and the elucidation of their biochemical outputs has organized funding in research, educational curricula, academic promotion, and the distribution of prestige through awards. Such reductionism has gone hand in hand with an ontology of the machine. We will discuss how viewing life as if it emanated from a set of molecular machines is the main bottleneck in addressing key questions in biology. We will discuss how moving beyond it is not contingent on new technologies but rather a refreshed perspective of life that can be termed \"organic\". Furthermore, we suggest that the study of how form arises, morphogenesis, is the key to an organic renewal of biology and biomedicine. Although morphogenesis is currently seen as a subsidiary branch of developmental biology as well as the consequence of molecular patterning processes at the subcellular scale, we will argue that morphology and its self-organizing capacity at the supracellular scale is the fundamental nexus in embryonic development as well as disease. We see the inability to appreciate form through an organic supracellular perspective as the principal bottleneck for making inroads into health issues such as cancer and the chronic disease epidemic.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"204018"},"PeriodicalIF":2.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617433","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":"Maternal control of embryonic dorsal organizer in vertebrates.","authors":"Jing Chen, Anming Meng","doi":"10.1016/j.cdev.2025.204020","DOIUrl":"10.1016/j.cdev.2025.204020","url":null,"abstract":"<p><p>The establishment of the body axis and developmental blueprint in embryos has remained to be a central question in developmental biology, captivating scientists for centuries. A milestone in this field was achieved in 1924 when Hans Spemann and Hilde Mangold discovered the dorsal organizer for embryonic body axis formation in amphibians. Since then, extensive studies have demonstrated that the dorsal organizer is evolutionarily conserved in vertebrates. This organizer functions as a signaling center, directing adjacent cells toward specific fates and orchestrating pattern formation to establish the embryonic axis. After 70 years since the discovery of the organizer, studies in different model animal species had revealed that locally activated β-catenin signaling during blastulation plays an indispensable role in organizer induction. Then, efforts have been made to identify initiators of β-catenin activation in blastulas. Now, it appears that maternal Huluwa, a transmembrane protein, is a bona fide organizer inducer at least in teleost fish and frog, which can activate downstream signaling pathways, including but probably not limited to β-catenin pathway. More studies are needed to decode the complete molecular network controlling organizer induction.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"204020"},"PeriodicalIF":2.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587391","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":"Mucociliary cell type compositions - bridging the gap between genes and emergent tissue functions.","authors":"Peter Walentek","doi":"10.1016/j.cdev.2025.204019","DOIUrl":"10.1016/j.cdev.2025.204019","url":null,"abstract":"<p><p>When multiple cell types are brought together to form a tissue-specific collective, the combination of cell functions and cell-cell interactions leads to novel behaviors and properties beyond the simple addition of individual features, often referred to as emergent tissue functions. During evolution, functional adaptations in organs are significantly influenced by changes in cell type compositions, and in diseases, aberrations in cell type compositions result in impaired organ functions. Investigating the mechanisms that regulate cell type compositions could elucidate an important organizational meta-level that bridges gene functions and cellular features de facto facilitating the emergence of collective cell behaviors and novel tissue functions. Due to their unique evolutionary positioning and diverse functions, mucociliary epithelia could provide an optimal system to unravel principle mechanisms of adaptations in cell type compositions that facilitate the evolution of new or optimization of existing tissue functions, and could reveal novel entry points to counteract human diseases. An integrative investigation of signaling, transcriptional, epigenetic and morphogenetic mechanisms across a broad range of mucociliary tissues with different specialized cells and cell type compositions can help us to connect gene functions and contributions to self-organized behaviors in cell collectives determining emergent tissue functions. Taking such route moving forward has the potential to unravel novel principles in mucociliary self-organization and to reveal broadly applicable principles underlying the generation and modification of emergent tissue functions across species and organ systems.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"204019"},"PeriodicalIF":2.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587340","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":"Cell biology of the chick organizer: Origins, composition, population dynamics and fate.","authors":"Claudio D Stern","doi":"10.1016/j.cdev.2025.204017","DOIUrl":"10.1016/j.cdev.2025.204017","url":null,"abstract":"<p><p>The year 2024 celebrates 100 years of perhaps one of the most important and influential papers in the field of developmental biology: Spemann and Mangold's publication reporting the discovery of the \"organizer\", which can induce and pattern the nervous system and also pattern the axial-lateral axis of the mesoderm. While many papers have investigated, and many others reviewed, the signalling aspects of the organizer, relatively fewer have concentrated on the cell biology of organizer cells. Here we survey more than 12 decades of knowledge on the chick organizer, including the cellular origins, fates, composition, cell movements, cell population properties and molecular dynamics of the chick organizer (the tip of the primitive streak). What emerges is a picture of an extremely complex and dynamic population of cells whose properties change over space and time, quite different from the \"textbook\" view of a static group of cells set aside during early development to perform a particular function in the normal embryo before being swept aside. Some of these findings also have more general implications for the interpretation of results from single cell RNA sequencing experiments.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"204017"},"PeriodicalIF":2.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568445","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, Run Yang, Tianyu Zhang, Jing Ma","doi":"10.1016/j.cdev.2025.204016","DOIUrl":"https://doi.org/10.1016/j.cdev.2025.204016","url":null,"abstract":"<p><p>Recent studies have identified pathogenic variants in the FOXI3 gene associated with craniofacial microsomia pedigrees. In zebrafish, the foxi1 gene is considered a functional homolog of the mouse Foxi3. However, research on foxi3a and foxi3b, 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 foxi3a or foxi3b 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 FOXI3 and highlight an unrecognized role of foxi3 in zebrafish CNCC and mandibular development.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"204016"},"PeriodicalIF":2.1,"publicationDate":"2025-02-28","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}
Arielle K Wolf, Lori C Adams-Phillips, Amanda N D Adams, Albert J Erives, Bryan T Phillips
{"title":"Nuclear localization and transactivation of SYS-1/β-catenin is the result of serial gene duplications and subfunctionalizations.","authors":"Arielle K Wolf, Lori C Adams-Phillips, Amanda N D Adams, Albert J Erives, Bryan T Phillips","doi":"10.1016/j.cdev.2025.204013","DOIUrl":"10.1016/j.cdev.2025.204013","url":null,"abstract":"<p><p>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, C. elegans 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.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"204013"},"PeriodicalIF":2.1,"publicationDate":"2025-02-25","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":"Dorsoventral patterning beyond the gastrulation stage: Interpretation of early dorsoventral cues and modular development mediated by zic1/zic4.","authors":"Toru Kawanishi, Hiroyuki Takeda","doi":"10.1016/j.cdev.2025.204012","DOIUrl":"10.1016/j.cdev.2025.204012","url":null,"abstract":"<p><p>Dorsoventral (DV) patterning is fundamental to vertebrate development, organizing the entire body across different germ layers. Although early DV axis formation, centered on the Spemann-Mangold organizer through the BMP activity gradient, has been extensively studied, the mechanisms shaping DV traits during later development remain largely unexplored. In this review, we highlight recent findings, especially from studies involving the Double anal fin (Da) spontaneous mutant of the small teleost medaka (Oryzias latipes), focusing on the roles of zic1 and zic4 (zic1/zic4) in regulating late DV patterning. These genes establish the dorsal domain of the trunk by converting the initial BMP gradient into distinct on/off spatial compartments within somites and their derivatives, acting as selector genes that define dorsal-specific traits, including myotome structure, body shape, and dorsal fin development. We also discuss how the zic-mediated dorsal domain is established and maintained from embryogenesis through adulthood. Furthermore, we provide evidence that zic-dependent action on the dorsal characteristics is dosage-dependent. We propose that the zic1/zic4-mediated DV patterning mechanism may represent a conserved regulatory framework that has been adapted to support the diverse body plans observed across vertebrate species.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"204012"},"PeriodicalIF":2.1,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516734","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}