Pub Date : 2026-01-08DOI: 10.1016/j.cdev.2026.204071
Shihao Yi , Juan Wen , Tianshun Wang , Wan Yu , Yanlin Liao , Zhengyun Liu , Huan Wang
Organoids are three-dimensional cellular structures formed through the self-organization of stem cells that mimic the structure and function of in vivo organs, offering broad applications in biomedical research. Mesenchymal stem cells (MSCs) are multipotent cells characterized by their self-renewal capacity and versatile biological roles, particularly in immunomodulation and angiogenesis promotion. While literature suggests that MSCs play a pivotal role in organoid formation, the precise mechanisms underlying this phenomenon remain elusive. In this review, we systematically dissect the dual roles of MSCs in organoid construction, including their direct contributions as initiating cells and indirect effects via immunomodulation and angiogenesis, while highlighting unresolved mechanistic questions and future translational potential.
{"title":"From initiation to maturation: Mesenchymal stem cells as key facilitators in organoid development","authors":"Shihao Yi , Juan Wen , Tianshun Wang , Wan Yu , Yanlin Liao , Zhengyun Liu , Huan Wang","doi":"10.1016/j.cdev.2026.204071","DOIUrl":"10.1016/j.cdev.2026.204071","url":null,"abstract":"<div><div>Organoids are three-dimensional cellular structures formed through the self-organization of stem cells that mimic the structure and function of in vivo organs, offering broad applications in biomedical research. Mesenchymal stem cells (MSCs) are multipotent cells characterized by their self-renewal capacity and versatile biological roles, particularly in immunomodulation and angiogenesis promotion. While literature suggests that MSCs play a pivotal role in organoid formation, the precise mechanisms underlying this phenomenon remain elusive. In this review, we systematically dissect the dual roles of MSCs in organoid construction, including their direct contributions as initiating cells and indirect effects via immunomodulation and angiogenesis, while highlighting unresolved mechanistic questions and future translational potential.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"185 ","pages":"Article 204071"},"PeriodicalIF":2.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939603","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}
Pub Date : 2025-12-13DOI: 10.1016/j.cdev.2025.204062
Isabelle Buisson , Jean-François Riou , Muriel Umbhauer , Ronan Le Bouffant , Valérie Bello
The functional organization of the vertebrate nephron is remarkably conserved, yet the morphogenetic processes underlying nephrogenesis vary across species and kidney types. The Xenopus larval kidney, the pronephros, is a non-integrated nephron where plasma filtrates are first released into a coelomic compartment, the nephrocoel, before entering the tubular compartment through ciliated nephrostomes. Mechanisms of pronephros morphogenesis, especially the role of the extracellular matrix (ECM), remain poorly understood. This study investigates the function of the ECM component versican (vcan) in the development of the pronephric kidney in X. laevis, focusing on non-integrated nephron features: the glomus, nephrocoel, and nephrostomes. Vcan is dynamically expressed in the ECM surrounding the developing tubule and the podocyte layer of the glomus, with transient presence in the differentiating podocyte region prior to the formation of the concave podocyte pocket that accumulates β1-integrin. Morpholino-mediated vcan depletion leads to fusion of proximal tubule branches, tubular dilation, and loss of proximal convolutions, without affecting nephrostomes. Glomus morphogenesis is severely disrupted, the podocyte layer fails to form its characteristic C-shaped structure, and β1-integrin fails to accumulate, although the podocyte differentiation marker nphs2 remains expressed. Other ECM components, including fibrillin, laminin, and fibronectin, remain correctly localized, indicating that the phenotype is not due to general ECM disorganization. Together, these findings identify a specific and temporally regulated role for vcan in glomus morphogenesis, likely by enabling β1-integrin accumulation and promoting cell–ECM interactions essential for proper podocyte layer assembly, thereby refining our understanding of ECM dynamics in kidney development.
{"title":"Transient versican expression is required for β1-integrin accumulation during podocyte layer morphogenesis in amphibian developing kidney","authors":"Isabelle Buisson , Jean-François Riou , Muriel Umbhauer , Ronan Le Bouffant , Valérie Bello","doi":"10.1016/j.cdev.2025.204062","DOIUrl":"10.1016/j.cdev.2025.204062","url":null,"abstract":"<div><div>The functional organization of the vertebrate nephron is remarkably conserved, yet the morphogenetic processes underlying nephrogenesis vary across species and kidney types. The <em>Xenopus</em> larval kidney, the pronephros, is a non-integrated nephron where plasma filtrates are first released into a coelomic compartment, the nephrocoel, before entering the tubular compartment through ciliated nephrostomes. Mechanisms of pronephros morphogenesis, especially the role of the extracellular matrix (ECM), remain poorly understood. This study investigates the function of the ECM component versican (vcan) in the development of the pronephric kidney in <em>X. laevis</em>, focusing on non-integrated nephron features: the glomus, nephrocoel, and nephrostomes. Vcan is dynamically expressed in the ECM surrounding the developing tubule and the podocyte layer of the glomus, with transient presence in the differentiating podocyte region prior to the formation of the concave podocyte pocket that accumulates β1-integrin. Morpholino-mediated vcan depletion leads to fusion of proximal tubule branches, tubular dilation, and loss of proximal convolutions, without affecting nephrostomes. Glomus morphogenesis is severely disrupted, the podocyte layer fails to form its characteristic C-shaped structure, and β1-integrin fails to accumulate, although the podocyte differentiation marker <em>nphs2</em> remains expressed. Other ECM components, including fibrillin, laminin, and fibronectin, remain correctly localized, indicating that the phenotype is not due to general ECM disorganization. Together, these findings identify a specific and temporally regulated role for vcan in glomus morphogenesis, likely by enabling β1-integrin accumulation and promoting cell–ECM interactions essential for proper podocyte layer assembly, thereby refining our understanding of ECM dynamics in kidney development.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"185 ","pages":"Article 204062"},"PeriodicalIF":2.0,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145764203","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}
Sarcopenia, characterized by an age-related decline in skeletal muscle mass and function, is closely associated with mitochondrial dysfunction. This study aimed to explore the role of myocyte enhancer factor 2A (MEF2A) in alleviating sarcopenia, focusing on its regulatory effect on mitochondrial homeostasis. AAV9-MEF2A was administered to 24-month-old male SAMP8 mice, and their endurance capacity and muscle histology were assessed. In vitro, MEF2A was overexpressed in C2C12 cells to examine its impact on myoblast proliferation and differentiation. Chromatin immunoprecipitation (ChIP), luciferase assays, and rescue experiments were conducted to identify downstream targets and validate the MEF2A-regulated signaling pathway. MEF2A overexpression significantly enhanced endurance performance, with a 1.17-fold increase in muscle mass, a 2.4 to 4.9-fold decrease in muscle atrophy markers compared to the AAV9-NC group, and a nearly 2 to 3-fold increase in mitochondrial biogenesis and antioxidant enzyme expression in aged mice. In C2C12 cells, MEF2A stimulated proliferation (1.8 fold increase in EdU-positive cells vs vector group) and differentiation (2 to 3-fold increase in differentiation markers vs vector group) while improving mitochondrial function through 1.5 to 2-fold increases in both OxPhos complex proteins and mitochondrial biogenesis genes compared to vector control. Mechanistically, MEF2A directly activated the PGC-1α/NRF2 axis, as validated by ChIP and reporter assays. Rescue experiments further verified the critical role of this pathway in MEF2A-mediated effects. These findings demonstrate that MEF2A mitigates sarcopenia by improving mitochondrial function and promoting muscle regeneration via activation of the PGC-1α/NRF2 signaling axis. MEF2A represents a promising therapeutic target for combating age-related muscle degeneration.
{"title":"A novel role of Mef2a in mitochondrial homeostasis and muscle regeneration during sarcopenia","authors":"Xin Tao , Suhong Zhang , Yue Li, Gongbing Tu, Dianfu Zhang, Liping Yin","doi":"10.1016/j.cdev.2025.204063","DOIUrl":"10.1016/j.cdev.2025.204063","url":null,"abstract":"<div><div>Sarcopenia, characterized by an age-related decline in skeletal muscle mass and function, is closely associated with mitochondrial dysfunction. This study aimed to explore the role of myocyte enhancer factor 2A (<em>MEF2A</em>) in alleviating sarcopenia, focusing on its regulatory effect on mitochondrial homeostasis. AAV9-<em>MEF2A</em> was administered to 24-month-old male SAMP8 mice, and their endurance capacity and muscle histology were assessed. In vitro, <em>MEF2A</em> was overexpressed in C2C12 cells to examine its impact on myoblast proliferation and differentiation. Chromatin immunoprecipitation (ChIP), luciferase assays, and rescue experiments were conducted to identify downstream targets and validate the <em>MEF2A</em>-regulated signaling pathway. MEF2A overexpression significantly enhanced endurance performance, with a 1.17-fold increase in muscle mass, a 2.4 to 4.9-fold decrease in muscle atrophy markers compared to the AAV9-NC group, and a nearly 2 to 3-fold increase in mitochondrial biogenesis and antioxidant enzyme expression in aged mice. In C2C12 cells, <em>MEF2A</em> stimulated proliferation (1.8 fold increase in EdU-positive cells vs vector group) and differentiation (2 to 3-fold increase in differentiation markers vs vector group) while improving mitochondrial function through 1.5 to 2-fold increases in both OxPhos complex proteins and mitochondrial biogenesis genes compared to vector control. Mechanistically, <em>MEF2A</em> directly activated the PGC-1α/NRF2 axis, as validated by ChIP and reporter assays. Rescue experiments further verified the critical role of this pathway in <em>MEF2A</em>-mediated effects. These findings demonstrate that <em>MEF2A</em> mitigates sarcopenia by improving mitochondrial function and promoting muscle regeneration via activation of the PGC-1α/NRF2 signaling axis. <em>MEF2A</em> represents a promising therapeutic target for combating age-related muscle degeneration.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"185 ","pages":"Article 204063"},"PeriodicalIF":2.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752132","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}
Pub Date : 2025-12-01DOI: 10.1016/j.cdev.2023.203897
Yagmur Azbazdar , Edgar M. Pera , Edward M. De Robertis
Neural induction by cell-cell signaling was discovered a century ago by the organizer transplantations of Spemann and Mangold in amphibians. Spemann later found that early dorsal blastopore lips induced heads and late organizers trunk-tail structures. Identifying region-specific organizer signals has been a driving force in the progress of animal biology. Head induction in the absence of trunk is designated archencephalic differentiation. Two specific head inducers, Cerberus and Insulin-like growth factors (IGFs), that induce archencephalic brain but not trunk-tail structures have been described previously. However, whether these two signals interact with each other had not been studied to date and was the purpose of the present investigation. It was found that Cerberus, a multivalent growth factor antagonist that inhibits Nodal, BMP and Wnt signals, strongly cooperated with IGF2, a growth factor that provides a positive signal through tyrosine kinase IGF receptors that activate MAPK and other pathways. The ectopic archencephalic structures induced by the combination of Cerberus and IGF2 are of higher frequency and larger than either one alone. They contain brain, a cyclopic eye and multiple olfactory placodes, without trace of trunk structures such as notochord or somites. A dominant-negative secreted IGF receptor 1 blocked Cerberus activity, indicating that endogenous IGF signals are required for ectopic brain formation. In a sensitized embryonic system, in which embryos were depleted of β-catenin, IGF2 did not by itself induce neural tissue while in combination with Cerberus it greatly enhanced formation of circular brain structures expressing the anterior markers Otx2 and Rx2a, but not spinal cord or notochord markers. The main conclusion of this work is that IGF provides a positive signal initially uniformly expressed throughout the embryo that potentiates the effect of an organizer-specific negative signal mediated by Cerberus. The results are discussed in the context of the history of neural induction.
{"title":"Head organizer: Cerberus and IGF cooperate in brain induction in Xenopus embryos","authors":"Yagmur Azbazdar , Edgar M. Pera , Edward M. De Robertis","doi":"10.1016/j.cdev.2023.203897","DOIUrl":"10.1016/j.cdev.2023.203897","url":null,"abstract":"<div><div>Neural induction by cell-cell signaling was discovered a century ago by the organizer transplantations of Spemann and Mangold in amphibians. Spemann later found that early dorsal blastopore lips induced heads and late organizers trunk-tail structures. Identifying region-specific organizer signals has been a driving force in the progress of animal biology. Head induction in the absence of trunk is designated archencephalic differentiation. Two specific head inducers, Cerberus and Insulin-like growth factors (IGFs), that induce archencephalic brain but not trunk-tail structures have been described previously. However, whether these two signals interact with each other had not been studied to date and was the purpose of the present investigation. It was found that Cerberus, a multivalent growth factor antagonist that inhibits Nodal, BMP and Wnt signals, strongly cooperated with IGF2, a growth factor that provides a positive signal through tyrosine kinase IGF receptors that activate MAPK and other pathways. The ectopic archencephalic structures induced by the combination of Cerberus and IGF2 are of higher frequency and larger than either one alone. They contain brain, a cyclopic eye and multiple olfactory placodes, without trace of trunk structures such as notochord or somites. A dominant-negative secreted IGF receptor 1 blocked Cerberus activity, indicating that endogenous IGF signals are required for ectopic brain formation. In a sensitized embryonic system, in which embryos were depleted of β-catenin, IGF2 did not by itself induce neural tissue while in combination with Cerberus it greatly enhanced formation of circular brain structures expressing the anterior markers <em>Otx2</em> and <em>Rx2a</em>, but not spinal cord or notochord markers. The main conclusion of this work is that IGF provides a positive signal initially uniformly expressed throughout the embryo that potentiates the effect of an organizer-specific negative signal mediated by Cerberus. The results are discussed in the context of the history of neural induction.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"184 ","pages":"Article 203897"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138810532","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}
Pub Date : 2025-12-01DOI: 10.1016/j.cdev.2025.204028
Rhanna R. Haantjes , Jeske Strik , Joëlle de Visser , Marten Postma , Renée van Amerongen , Antonius L. van Boxtel
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.
{"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":"10.1016/j.cdev.2025.204028","url":null,"abstract":"<div><div>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 <em>in vitro</em> 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.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"184 ","pages":"Article 204028"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","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}
Pub Date : 2025-12-01DOI: 10.1016/j.cdev.2024.203991
Denis Duboule, Hocine Rekaik
2024 not only marked the 100th anniversary of the discovery of the organizer by Hilde Pröscholdt-Mangold and Hans Spemann, but also the 40th anniversary of the discovery of the homeobox, a DNA region encoding a DNA binding peptide present in several transcription factors of critical importance for the gastrulating embryo. In particular, this sequence is found in the 39 members of the amniote Hox gene family, a series of genes activated in mid-gastrulation and involved in organizing morphologies along the extending anterior to posterior (AP) body axis. Over the past 30 years, the study of their coordinated regulation in various contexts has progressively revealed their surprising regulatory strategies, based on mechanisms acting in-cis, which can translate a linear distribution of series of genes along the chromatin fiber into the proper sequences of morphologies observed along our various body axes. The first regulatory layer is controlled by the Hox timer, a mechanism implementing a time-sequenced activation of these genes following their chromosomal order. Here, we discuss various aspects of this mechanism, emphasizing some of its singularities.
{"title":"Comments on the Hox timer and related issues","authors":"Denis Duboule, Hocine Rekaik","doi":"10.1016/j.cdev.2024.203991","DOIUrl":"10.1016/j.cdev.2024.203991","url":null,"abstract":"<div><div>2024 not only marked the 100th anniversary of the discovery of the organizer by Hilde Pröscholdt-Mangold and Hans Spemann, but also the 40th anniversary of the discovery of the homeobox, a DNA region encoding a DNA binding peptide present in several transcription factors of critical importance for the gastrulating embryo. In particular, this sequence is found in the 39 members of the amniote <em>Hox</em> gene family, a series of genes activated in mid-gastrulation and involved in organizing morphologies along the extending anterior to posterior (AP) body axis. Over the past 30 years, the study of their coordinated regulation in various contexts has progressively revealed their surprising regulatory strategies, based on mechanisms acting in-cis, which can translate a linear distribution of series of genes along the chromatin fiber into the proper sequences of morphologies observed along our various body axes. The first regulatory layer is controlled by the <em>Hox</em> timer, a mechanism implementing a time-sequenced activation of these genes following their chromosomal order. Here, we discuss various aspects of this mechanism, emphasizing some of its singularities.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"184 ","pages":"Article 203991"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903646","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}
Pub Date : 2025-12-01DOI: 10.1016/j.cdev.2024.203988
Wouter Masselink , Prayag Murawala
Chordate tail regeneration represents the remarkable ability of some chordates to partially or completely regenerate a significant portion of their primary body axis. In this review we will discuss the chordate regenerative ability, what is known about the cellular sources which contribute to the regenerating tail, how various structures such as the spinal cord and vertebral column are re-established, and how scaling of the regenerating tail is regulated. Finally, we propose that tail regeneration is evolutionarily conserved and is fundamentally different from tail development however the origin and mechanism of this process remain elusive.
{"title":"The evolutionary origin and mechanism of chordate tail regeneration. An ancient tale?","authors":"Wouter Masselink , Prayag Murawala","doi":"10.1016/j.cdev.2024.203988","DOIUrl":"10.1016/j.cdev.2024.203988","url":null,"abstract":"<div><div>Chordate tail regeneration represents the remarkable ability of some chordates to partially or completely regenerate a significant portion of their primary body axis. In this review we will discuss the chordate regenerative ability, what is known about the cellular sources which contribute to the regenerating tail, how various structures such as the spinal cord and vertebral column are re-established, and how scaling of the regenerating tail is regulated. Finally, we propose that tail regeneration is evolutionarily conserved and is fundamentally different from tail development however the origin and mechanism of this process remain elusive.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"184 ","pages":"Article 203988"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872630","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}
Embryonic development is a complex self-organizing process orchestrated by a series of regulatory events at the molecular and cellular levels, resulting in the formation of a fully functional organism. This review focuses on activin protein as a mesoderm-inducing factor and the self-organizing properties it confers. Activin has been detected in both unfertilized eggs and embryos, suggesting its involvement in early developmental processes. To explore its effects, animal cap cells—pluripotent cells from the animal pole of amphibian blastula-stage embryos—were treated with varying concentrations of activin. The results showed that activin induced mesodermal tissues, including blood, muscle, and notochord, in a dose-dependent manner. Co-treatment with activin and retinoic acid further promoted the development of kidney and pancreatic tissues, while activin alone stimulated the formation of beating cardiac tissue. In subsequent experiments, high concentrations of activin conferred an organizer-like activity on animal cap cells. The pretreatment duration affected outcomes: longer exposure induced anterior structures, such as eyes, while shorter exposure resulted in posterior structures, like tails. These findings reflect moderate self-assembly, where cells become increasingly organized. In another experiment, activin was used to create an artificial gradient. Explants cultured on this gradient developed into embryoids with well-defined anteroposterior, dorsoventral, and left-right axes, exemplifying higher-order self-organization. These results demonstrate that controlled activin gradients can drive the formation of nearly complete tadpole-like larvae, effectively recapitulating the processes of early embryogenesis. This system offers valuable insights into the mechanisms underlying axis formation and organogenesis, providing a promising platform for future research in developmental biology.
{"title":"Self-organization from organs to embryoids by activin in early amphibian development","authors":"Makoto Asashima , Yumeko Satou-Kobayashi , Yoshikazu Haramoto , Takashi Ariizumi","doi":"10.1016/j.cdev.2025.203996","DOIUrl":"10.1016/j.cdev.2025.203996","url":null,"abstract":"<div><div>Embryonic development is a complex self-organizing process orchestrated by a series of regulatory events at the molecular and cellular levels, resulting in the formation of a fully functional organism. This review focuses on activin protein as a mesoderm-inducing factor and the self-organizing properties it confers. Activin has been detected in both unfertilized eggs and embryos, suggesting its involvement in early developmental processes. To explore its effects, animal cap cells—pluripotent cells from the animal pole of amphibian blastula-stage embryos—were treated with varying concentrations of activin. The results showed that activin induced mesodermal tissues, including blood, muscle, and notochord, in a dose-dependent manner. Co-treatment with activin and retinoic acid further promoted the development of kidney and pancreatic tissues, while activin alone stimulated the formation of beating cardiac tissue. In subsequent experiments, high concentrations of activin conferred an organizer-like activity on animal cap cells. The pretreatment duration affected outcomes: longer exposure induced anterior structures, such as eyes, while shorter exposure resulted in posterior structures, like tails. These findings reflect moderate self-assembly, where cells become increasingly organized. In another experiment, activin was used to create an artificial gradient. Explants cultured on this gradient developed into embryoids with well-defined anteroposterior, dorsoventral, and left-right axes, exemplifying higher-order self-organization. These results demonstrate that controlled activin gradients can drive the formation of nearly complete tadpole-like larvae, effectively recapitulating the processes of early embryogenesis. This system offers valuable insights into the mechanisms underlying axis formation and organogenesis, providing a promising platform for future research in developmental biology.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"184 ","pages":"Article 203996"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042591","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}
Pub Date : 2025-12-01DOI: 10.1016/j.cdev.2025.204020
Jing Chen , Anming Meng
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.
{"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":"<div><div>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.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"184 ","pages":"Article 204020"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","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}
Pub Date : 2025-12-01DOI: 10.1016/j.cdev.2025.204017
Claudio D. Stern
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.
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