{"title":"Biophysical, cellular, and mouse model approaches to investigate the mechanical regulation of folliculogenesis","authors":"Sara Pietroforte, Farners Amargant","doi":"10.1016/j.semcdb.2025.103649","DOIUrl":"10.1016/j.semcdb.2025.103649","url":null,"abstract":"<div><div>Folliculogenesis, which is the process by which ovarian follicles develop to support oogenesis and hormone production, is essential for female fertility. Although hormonal and biochemical signaling pathways regulating folliculogenesis have been extensively studied, increasing evidence suggests that mechanical cues within the ovary also play a critical role. The ovary is composed of follicles, corpora lutea, and stroma, each contributing to a biomechanical microenvironment that might change across the reproductive lifespan. Additionally, the spatial organization of the ovary, with a collagen-rich cortex and a softer medulla, may influence follicle activation and growth. This review explores the hypothesis that mechanical properties of the ovary regulate folliculogenesis, integrating current knowledge on ovarian architecture, extracellular matrix composition, and mechanotransduction pathways. We highlight recent findings supporting mechanical regulation of folliculogenesis, discuss contradictory data, and describe the tools and models used to investigate this concept. By considering mechanical forces alongside hormonal and biochemical signals, we propose a more integrated view of the factors governing follicle development, with implications for understanding ovarian physiology and pathology.</div></div>","PeriodicalId":21735,"journal":{"name":"Seminars in cell & developmental biology","volume":"174 ","pages":"Article 103649"},"PeriodicalIF":6.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144920273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elie N. Farah , Jessyka T. Diaz , Joshua Bloomekatz , Neil C. Chi
{"title":"Charting the cardiac landscape: Advances in spatial transcriptomics for heart biology","authors":"Elie N. Farah , Jessyka T. Diaz , Joshua Bloomekatz , Neil C. Chi","doi":"10.1016/j.semcdb.2025.103648","DOIUrl":"10.1016/j.semcdb.2025.103648","url":null,"abstract":"<div><div>The heart is the first organ to form in the developing embryo. Throughout development, it continues to grow and function to support the maturing fetus by circulating nutrients to all of the developing organs. Defects in the spatial organization of cardiac cells can lead to congenital heart defects (CHD), which affects 1–3 % of all live births, as well as adult heart diseases. Spatial transcriptomics has revolutionized our understanding of cardiac biology by providing high-resolution maps of gene expression within intact tissue, offering insights into cellular interactions and spatial organization across the entire heart. Recent improvements have enabled precise mapping of cellular heterogeneity within developing human hearts, revealing spatially organized populations of cardiomyocytes and non-cardiomyocyte cells and key signaling pathways in cardiac morphogenesis. Studies of adult hearts post-myocardial infarction (MI) using these technologies have unraveled gene expression patterns specific to injury zones. Furthermore, multi-modal approaches combining spatial transcriptomics with epigenetic, proteomic, and functional data have expanded our understanding of cell type-specific responses and molecular mechanisms underpinning cardiac injury responses and fibrosis. Here, we describe the range of spatial transcriptomic technologies currently available and discuss the technical considerations involved in conducting spatial analyses. We further highlight the progression from early spatial mapping techniques to contemporary high-resolution, multi-modal approaches in studying cardiac tissue, underscoring how these advancements provide unprecedented insights into heart development, disease, and regeneration, and discuss future directions for applying spatial transcriptomics to address fundamental questions in cardiovascular biology and therapy.</div></div>","PeriodicalId":21735,"journal":{"name":"Seminars in cell & developmental biology","volume":"175 ","pages":"Article 103648"},"PeriodicalIF":6.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Suhrid Ghosh , Chandrashekar Kuyyamudi , Beatrice L. Steinert , Cassandra G. Extavour
{"title":"Mechanical mechanisms of morphogenesis as potential substrates for evolutionary change","authors":"Suhrid Ghosh , Chandrashekar Kuyyamudi , Beatrice L. Steinert , Cassandra G. Extavour","doi":"10.1016/j.semcdb.2025.103645","DOIUrl":"10.1016/j.semcdb.2025.103645","url":null,"abstract":"<div><div>The first quarter of this century has seen a resurgence of interest in the mechanical and physical mechanisms that drive cellular behaviors in the context of morphogenesis. Far from being a new discovery, the fact that the material properties of cells and the physical forces that they exert and experience must play decisive roles in development, was an important part of the field of experimental embryology well over a century ago. Following the birth of molecular biology, and the development of live imaging approaches that can capture the dynamics of both cellular properties and materials, and the activity of genes and gene products, the current manifestation of this field promises to link mechanical and molecular genetic mechanisms. Here we review recent advances in understanding the relationships between mechanical and molecular genetic mechanisms, and suggest paths forward that could yield answers to the pressing questions of whether and how evolutionary forces act not only on functional morphologies, but also on the mechanical forces that create them.</div></div>","PeriodicalId":21735,"journal":{"name":"Seminars in cell & developmental biology","volume":"175 ","pages":"Article 103645"},"PeriodicalIF":6.0,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanistic modeling of mitosis: Insights from three collaborative case studies","authors":"Jing Chen , Daniela Cimini","doi":"10.1016/j.semcdb.2025.103643","DOIUrl":"10.1016/j.semcdb.2025.103643","url":null,"abstract":"<div><div>Mechanistic mathematical modeling has become an essential tool in modern biological research due to its powerful ability to integrate diverse data, generate hypotheses, and guide experimental design. It is particularly valuable for studying complex cellular mechanisms involving numerous interacting components. While the full dynamics of such systems usually elude direct experimental observation, modeling provides a means to integrate fragmented data with reasonable and/or informed assumptions into coherent mechanistic frameworks, simulate system behavior, and identify promising directions for further experimentation. When closely integrated with experiments, modeling can greatly accelerate progress in cell biology. However, the value of modeling is not automatic—it must be earned through careful model construction, critical interpretation of results, and thoughtful design of follow-up experiments. To demystify this process, we review three of our collaborative projects in mitosis, drawing on our experiences as a modeler and an experimentalist. We describe how the projects were initiated, why specific modeling approaches were chosen, how models were developed and refined, how model predictions guided new experiments, and how integrated modeling and experimentation led to deeper mechanistic insights. Finally, we emphasize that at the heart of every successful collaboration lies human connection. Productive cross-disciplinary communication is fundamental to bridging experimental and modeling perspectives and fully realizing the potential of integrative approaches in modern cell biology.</div></div>","PeriodicalId":21735,"journal":{"name":"Seminars in cell & developmental biology","volume":"175 ","pages":"Article 103643"},"PeriodicalIF":6.0,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The mechanics behind the Drosophila egg","authors":"Megha Maria Jacob, Muriel Grammont","doi":"10.1016/j.semcdb.2025.103638","DOIUrl":"10.1016/j.semcdb.2025.103638","url":null,"abstract":"<div><div>The formation and the development of the <em>Drosophila</em> egg involves multiple mechanical cross-talks between germline cells, somatic cells and the surrounding basement membrane. In this review, we discuss several development stages when the sources, as well as the roles, of mechanical forces in egg shape establishment are well defined. The examples described here illustrate the diversity of these forces as well as of the tools used to measure them and of the outcome each of them generates. We examine their contributions and their integration to morphogenesis. We discuss the limitations of our current knowledge, the importance of developing novel approaches and the support that modelling could bring to tackle some issues. One major future challenge is to understand how robustness in shaping the egg is achieved when the contributors act in different cell types and at different times. Studying <em>Drosophila</em> egg formation thus remains an exciting model in developmental biology as it must integrate a variety of biomechanical inputs from its environment, in addition of the biochemical signals discovered in the past.</div></div>","PeriodicalId":21735,"journal":{"name":"Seminars in cell & developmental biology","volume":"175 ","pages":"Article 103638"},"PeriodicalIF":6.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144878521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanics of oogenesis: Lessons from C. elegans germline cysts","authors":"Kenji Kimura, Fumio Motegi","doi":"10.1016/j.semcdb.2025.103644","DOIUrl":"10.1016/j.semcdb.2025.103644","url":null,"abstract":"<div><div>Germ cells are organized into a syncytial architecture, wherein individual cells remain connected via intercellular bridges. Within this structural framework, known as germline cysts, a subset of germ cells enlarges and develops into oocytes, while others shrink and are eliminated through cell death. Recent studies with <em>Caenorhabditis elegans</em> have revealed that both apoptosis-mediated germ cell death and enlargement of surviving germ cells are regulated by mechanical forces. Germ cells exhibit stochastic fluctuations in volume driven by actomyosin contractility. This initial size heterogeneity is progressively amplified due to mechanical instability driven by differential hydrostatic pressure within the cyst, which biases smaller cells toward shrinkage and subsequent apoptotic death. This mechanical instability is further reinforced by the RAS/MAPK signaling cascade and the ECT-2/RhoA pathway, both of which enhance actomyosin contractility. Surviving germ cells continue to grow by acquiring the cytoplasmic materials through actomyosin contractility-mediated hydrodynamic flow within the cyst. Collectively, these findings highlight the critical role of mechanical forces in modulating cell fate decisions between survival and death, facilitating cell volume dynamics and maintaining germline homeostasis during oogenesis.</div></div>","PeriodicalId":21735,"journal":{"name":"Seminars in cell & developmental biology","volume":"175 ","pages":"Article 103644"},"PeriodicalIF":6.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144886523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Arezoo Dadashzadeh , Saeid Moghassemi , Saba Nikanfar , Ellen C.R. Leonel , Shunran Zhang , Maria João Sousa , Thalles Fernando Rocha Ruiz , Christiani A. Amorim
{"title":"Engineering the ovarian niche: Environmental control of folliculogenesis in vitro","authors":"Arezoo Dadashzadeh , Saeid Moghassemi , Saba Nikanfar , Ellen C.R. Leonel , Shunran Zhang , Maria João Sousa , Thalles Fernando Rocha Ruiz , Christiani A. Amorim","doi":"10.1016/j.semcdb.2025.103639","DOIUrl":"10.1016/j.semcdb.2025.103639","url":null,"abstract":"<div><div>Advancements in cancer therapies have significantly improved patient survival, but gonadotoxic treatments often compromise fertility, particularly in female patients. While ovarian tissue cryopreservation and transplantation are well-established fertility preservation options, they are not recommended for patients with blood-borne cancers or highly metastatic malignancies due to the risk of ovarian involvement. In these cases, follicle in vitro culture offers a promising alternative. However, folliculogenesis is a complex process that requires meticulous environmental control to mimic the ovarian niche. Key factors include biochemical signals delivered through culture media, biophysical support provided by three-dimensional biomaterials or the native extracellular matrix, and crucial cellular interactions that drive follicular development. Recent advances in biomaterial design have led to the creation of scaffolds that not only preserve structural integrity but also facilitate nutrient exchange and cell communication. Moreover, dynamic culture systems have shown superior outcomes compared to static models, offering a more physiologically relevant environment. This review explores the interplay of biochemical, biophysical, and mechanical factors in in vitro folliculogenesis. By synthesizing current innovations in scaffold design, culture systems, and bioactive supplementation, we outline key strategies for optimizing in vitro follicular development. These advances pave the way toward safer and more effective fertility preservation approaches for patients at high risk of ovarian metastasis and offer broader insights into reproductive biology and regenerative medicine. However, to fully realize this potential, further standardization, long-term safety studies, and critical evaluation of emerging technologies remain essential to enable robust clinical translation and personalized reproductive applications.</div></div>","PeriodicalId":21735,"journal":{"name":"Seminars in cell & developmental biology","volume":"175 ","pages":"Article 103639"},"PeriodicalIF":6.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144867375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The mechanics of shaping organs in plants","authors":"Ankita Dash , Mabel Maria Mathew , Kalika Prasad","doi":"10.1016/j.semcdb.2025.103640","DOIUrl":"10.1016/j.semcdb.2025.103640","url":null,"abstract":"<div><div>Mechanical forces are instrumental to shaping lifeforms, influencing development from the subcellular scale to the organismal scale. Here, we explore how mechanical forces manifest themselves in plants, driving deformations such as tissue folding, buckling, undulating patterns, and edge curving. These deformations result from modulations in fundamental cellular processes such as cell division, cell expansion, cell wall mechanics, and cytoskeletal organization. Cytoskeletal structure like microtubules, actin filaments respond to mechanical cues by generating localized stress patterns that shape cell structure and function. Mechanical forces can also regulate gene expression and gate mechanosensitive channels to regulate ion fluxes, thereby integrating physical forces with biochemical properties. We draw parallels between plant and animal kingdoms to show how these two kingdoms utilize mechanochemical effects to drive growth and morphogenesis.</div></div>","PeriodicalId":21735,"journal":{"name":"Seminars in cell & developmental biology","volume":"175 ","pages":"Article 103640"},"PeriodicalIF":6.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144813846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kosei Tomida , Huan Ting Ong , Jennifer L. Young , Chii Jou Chan
{"title":"Capturing ovarian dynamics through spatial profiling of the mechano-microenvironment","authors":"Kosei Tomida , Huan Ting Ong , Jennifer L. Young , Chii Jou Chan","doi":"10.1016/j.semcdb.2025.103642","DOIUrl":"10.1016/j.semcdb.2025.103642","url":null,"abstract":"<div><div>In recent years, tissue mechanics has been recognized not as a passive outcome of development but may function as upstream regulators to guide cellular functions such as proliferation, migration, and differentiation. In mammalian ovaries, cross-scale mechanical signals arising from tissue deformation, extracellular matrix architecture, and intrafollicular pressure dynamically evolve over the reproductive lifespan, contributing to a complex biomechanical landscape. Despite increasing recognition of their role in regulating follicle development, mechanical signals from ovarian microenvironment are still often considered separately from changes in gene expression and metabolic pathways. In addition, comprehensive mapping of the ovarian mechano-microenvironment remains lacking, in part due to challenges in assessing mechanical information in ovaries. Here we discuss how emerging biophysical techniques, including the latest advancement in various omics technologies, allow us to probe ovarian mechanics across multiple length scales. Such an integrated approach will provide new insights on how force transmission, matrix remodeling, and cellular signaling intersect within defined spatial niches to regulate ovarian dynamics, paving the way for future understanding of the mechanobiological basis of reproductive disorders.</div></div>","PeriodicalId":21735,"journal":{"name":"Seminars in cell & developmental biology","volume":"175 ","pages":"Article 103642"},"PeriodicalIF":6.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144813799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evolvability in vertebrate segmentation","authors":"James E. Hammond, Callum V. Bucklow, Berta Verd","doi":"10.1016/j.semcdb.2025.103630","DOIUrl":"10.1016/j.semcdb.2025.103630","url":null,"abstract":"<div><div>The number of vertebrae in the axial skeleton of vertebrates is extremely diverse, and reflects adaptations to a diverse range of habitats and lifestyles. The capacity for heritable evolutionary change in the number of vertebrae — its evolvability — is underpinned by the process of somitogenesis, which determines the number of somites that form in the early embryo. However, despite the evolvability of somitogenesis having been crucial for the success of the vertebrates across evolutionary history, the developmental sources of evolvability in somitogenesis are still unknown. Here, we review the evolution of somitogenesis and vertebral number, and attempt to identify sources of evolvability within this important developmental process.</div></div>","PeriodicalId":21735,"journal":{"name":"Seminars in cell & developmental biology","volume":"174 ","pages":"Article 103630"},"PeriodicalIF":6.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144779974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}