{"title":"Signalling molecules and microenvironment modulation in skin regeneration of chronic wound repair: A cellular perspective.","authors":"Keren Celestina Mendonce, Naveen Palani, P Monisha, Parthasarathy Surya, Suriyaprakash Rajadesingu","doi":"10.1016/j.cdev.2025.204053","DOIUrl":"https://doi.org/10.1016/j.cdev.2025.204053","url":null,"abstract":"<p><p>Tissue repair is an intricate biological process involving cellular and molecular mechanisms. These mechanisms coordinate the repair of damaged tissue, relying on the function of several signalling molecules. Growth factors, cytokines, and hormones perform a fundamental role in tissue regeneration, especially in skin regeneration. On the other hand, in case of diabetes or chronic wounds, the synthesis and regulation of these signalling molecules may be disrupted. Despite advances in medical science, chronic, non-healing wounds remain a continuous challenge, often characterized by reduced angiogenesis, impaired epithelialization, irregular granulation tissue formation, and elevated inflammation. This highlights the need to explore their therapeutic applications and the possibility of external production or stimulation for improved healing. The cellular intricacies are revealed within the wounded environment, explaining the functions of each signalling molecule, thus providing a roadmap for therapeutic exploration. It scrutinizes the complexities of venous and arterial ulcers, diabetic wounds, and complex burn wounds, which indicates the urgency of coming up with innovative interventions. From the modulation of wound microenvironments will arise new treatment modalities that spur tissue restoration with efficacy. Scientists have explored the wound healing properties of Vascular Endothelial Growth Factor, Platelet Derived Growth Factor, Transforming Growth Factor-β, granulocyte-macrophage colony-stimulating factor, estradiol benzoate, thyroxine, and erythropoietin. This review article acts as a guide for better treatments that can improve wound healing.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"204053"},"PeriodicalIF":2.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213934","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":"Coordinating tissue development to build body and brain: Lessons from the gastrula organiser and its derivatives.","authors":"Alexandra Neaverson, Benjamin Steventon","doi":"10.1016/j.cdev.2025.204042","DOIUrl":"10.1016/j.cdev.2025.204042","url":null,"abstract":"<p><p>The Spemann-Mangold organiser has been a central paradigm in developmental biology for over a century, primarily studied through its ability to induce secondary axes in transplantation experiments. However, how the organiser and its derivatives act together to generate a well-proportioned body axis is still unknown. Here, we review evidence across four major vertebrate models (Xenopus, zebrafish, chick, and mouse) to evaluate the organiser's stage-specific requirements in neural development and body axis formation. We present a consensus view that initial neural specification and anterior-posterior patterning occur before morphological organiser formation, driven by planar signals from pre-organiser cells and species-specific contributions from extraembryonic tissues. We also discuss how the organiser-derived anterior axial mesendoderm (prechordal plate and head process) primarily acts to maintain anterior identity and ensure proper tissue proportions through continued signalling. The posterior organiser derivative, the notochord, remains essential for dorsal-ventral neural patterning, but also coordinates posterior body elongation through mechanical coupling with adjacent tissues, and the pace of axial mesoderm extension serves as a key coordinator of proportional body axis development. Future studies will improve our understanding of how organiser derivatives orchestrate the mechanical and molecular coordination of multiple tissues during axis formation.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"204042"},"PeriodicalIF":2.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718790","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}
Alfonso Martinez Arias, André Dias, Alexandra E Wehmeyer, Sebastian J Arnold, Ulla-Maj Fiúza
{"title":"A modular organization of mammalian gastrulation and the Spemann-Mangold organizer.","authors":"Alfonso Martinez Arias, André Dias, Alexandra E Wehmeyer, Sebastian J Arnold, Ulla-Maj Fiúza","doi":"10.1016/j.cdev.2025.204031","DOIUrl":"10.1016/j.cdev.2025.204031","url":null,"abstract":"<p><p>Studies in amphibian embryos revealed the existence of groups of cells, organizers, that play a central role in laying down the body plan. One, the Spemann-Mangold Organizer (SMO) is associated with the induction of the nervous system and the development of the head, whereas a second one has been linked with the development of the trunk and the tail. Homologues of these organizers have been described in other vertebrates. In the mouse, the SMO organizer has been associated with a region of the mid- early gastrula and the tail-trunk Organizer with the node. Altogether these observations suggest a modular organization of the vertebrate body plan into three domains. One, most anterior, competent to form the brain, a middle one, associated with neural induction and the head, and one dedicated to axial extension. Work with gastruloids, pluripotent stem cell models of mammalian development, reveal that these modules are independent developmental units. Here we discuss the relationship of the gastruloids findings to the activity of organizers in embryos and the implications of this modular organization for the evolution of the vertebrate body plan.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"204031"},"PeriodicalIF":2.1,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142541","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}
Rhanna R Haantjes, Jeske Strik, Joëlle de Visser, Marten Postma, Renée van Amerongen, Antonius L van Boxtel
{"title":"Towards an integrated view and understanding of embryonic signalling during murine gastrulation.","authors":"Rhanna R Haantjes, Jeske Strik, Joëlle de Visser, Marten Postma, Renée van Amerongen, Antonius L van Boxtel","doi":"10.1016/j.cdev.2025.204028","DOIUrl":"https://doi.org/10.1016/j.cdev.2025.204028","url":null,"abstract":"<p><p>At the onset of mammalian gastrulation, secreted signalling molecules belonging to the Bmp, Wnt, Nodal and Fgf signalling pathways induce and pattern the primitive streak, marking the start for the cellular rearrangements that generate the body plan. Our current understanding of how signalling specifies and organises the germ layers in three dimensions, was mainly derived from genetic experimentation using mouse embryos performed over many decades. However, the exact spatiotemporal sequence of events is still poorly understood, both because of a lack of tractable models that allow for real time visualisation of signalling and differentiation and because of the molecular and cellular complexity of these early developmental events. In recent years, a new wave of in vitro embryo models has begun to shed light on the dynamics of signalling during primitive streak formation. Here we discuss the similarities and differences between a widely adopted mouse embryo model, termed gastruloids, and real embryos from a signalling perspective. We focus on the gene regulatory networks that underlie signalling pathway interactions and outline some of the challenges ahead. Finally, we provide a perspective on how embryo models may be used to advance our understanding of signalling dynamics through computational modelling.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"204028"},"PeriodicalIF":2.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985329","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":"Self-organization of an organizer: Whole-body regeneration from reaggregated cells in cnidarians.","authors":"Sanjay Narayanaswamy, Ulrich Technau","doi":"10.1016/j.cdev.2025.204024","DOIUrl":"10.1016/j.cdev.2025.204024","url":null,"abstract":"<p><p>Cnidarians like the freshwater polyp Hydra and the sea anemone Nematostella, are famous for their enormous capacity to regenerate missing head or feet upon bisection. Classical transplantation experiments have demonstrated that the hypostome, the oral tip of the freshwater polyp Hydra, acts as an axial organizer. Likewise, transplantation of the blastopore lip of an early Nematostella gastrula stage embryo to an aboral position leads to ectopic head formation. Following molecular analyses have shown that Wnt signaling is the key component of this organizer activity. Moreover, when dissociated and reaggregated head (and foot) organizer centres are re-established by self-organization. Similarly, \"gastruloids\", i.e. aggregates of dissociated early gastrula stage embryos, are able to self-organize. Here, we review the past and recent molecular and theoretical work in the field to explain this phenomenon. While Turing-type reaction-diffusion models involving morphogens like Wnt dominated the field for many years, recent work emphasized the importance of biophysical cues in symmetry breaking and establishment of the organizers in aggregates. The comparison with Nematostella aggregates suggests that the principles of self-organization in cnidarians is not universal.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"204024"},"PeriodicalIF":2.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781522","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":"10.1016/j.cdev.2025.204022","url":null,"abstract":"<p><p>Epithelia are ubiquitous tissues with essential structural, signaling, and barrier functions. How cells transition from individual to collective behaviors as they build and remodel epithelia throughout development is a fundamental question in developmental biology. Recent studies show that three-dimensional multicellular rosettes are key intermediates that provide a solution to the challenge of building tissue-scale epithelia by coordinating local interactions in small groups of cells. These radially polarized rosette structures facilitate epithelial formation by providing a protected environment for cells to acquire apical-basal polarity, establish cell adhesion, and coordinate intercellular signaling. Once formed, rosettes can dynamically expand, move, coalesce, and interact with surrounding tissues to generate a wide range of structures with specialized functions, including epithelial sheets, tubes, cavities, and branched networks. In this review, we describe the mechanisms that regulate rosette assembly and dynamics, and discuss how rosettes serve as versatile intermediates in epithelial morphogenesis. In addition, we present open questions about the molecular, cellular, and biophysical mechanisms that drive rosette behaviors, and discuss the implications of this widely used 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}