Cells and Development最新文献

Transient versican expression is required for β1-integrin accumulation during podocyte layer morphogenesis in amphibian developing kidney 在两栖动物肾脏发育过程中足细胞层形态发生过程中β1-整合素的积累需要瞬时型表达。

IF 2 4区生物学 Q4 Biochemistry, Genetics and Molecular Biology

Cells and Development

Pub Date : 2025-12-13 DOI: 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.

脊椎动物肾元的功能组织是非常保守的，然而肾形成的形态发生过程在不同物种和肾类型之间是不同的。爪蟾幼体肾脏（原肾）是一个非整合肾元，血浆滤液首先被释放到体腔室（肾腔），然后通过纤毛肾造口进入肾小管室。原肾形态发生的机制，特别是细胞外基质（ECM）的作用，仍然知之甚少。本研究探讨了ECM组分versican （vcan）在肾小球肾小球形成中的功能，重点关注非整合肾元特征：肾小球、肾结和肾造口。Vcan在发育中的小管和足细胞层周围的ECM中动态表达，在形成凹形足细胞袋积聚β1-整合素之前，在分化的足细胞区短暂存在。morpholinos介导的vcan耗竭导致近端小管分支融合、小管扩张和近端曲丢失，而不影响肾造口。尽管足细胞分化标记物nphs2仍有表达，但球囊形态发生严重破坏，足细胞层不能形成其特有的c形结构，β1-整合素不能积累。其他ECM成分，包括原纤维蛋白，层粘连蛋白和纤维连接蛋白，仍然正确定位，表明表型不是由于一般的ECM紊乱。总之，这些发现确定了vcan在肾小球形态发生中的特定和暂时调节作用，可能是通过促进β1-整合素积累和促进细胞-ECM相互作用，这是足细胞层适当组装所必需的，从而完善了我们对肾脏发育中ECM动力学的理解。

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引用次数: 0

A novel role of Mef2a in mitochondrial homeostasis and muscle regeneration during sarcopenia Mef2a在肌肉减少症期间线粒体稳态和肌肉再生中的新作用。

IF 2 4区生物学 Q4 Biochemistry, Genetics and Molecular Biology

Cells and Development

Pub Date : 2025-12-11 DOI: 10.1016/j.cdev.2025.204063

Xin Tao , Suhong Zhang , Yue Li, Gongbing Tu, Dianfu Zhang, Liping Yin

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.

骨骼肌减少症的特征是骨骼肌质量和功能与年龄相关的下降，与线粒体功能障碍密切相关。本研究旨在探讨肌细胞增强因子2A （myocyte enhancer factor 2A, MEF2A）在缓解肌少症中的作用，重点关注其对线粒体稳态的调节作用。给予24月龄雄性SAMP8小鼠AAV9-MEF2A，评估其耐力和肌肉组织学。体外，MEF2A在C2C12细胞中过表达，检测其对成肌细胞增殖和分化的影响。通过染色质免疫沉淀（ChIP）、荧光素酶测定和救援实验来确定下游靶点并验证mef2a调节的信号通路。MEF2A过表达显著提高了耐力表现，与AAV9-NC组相比，老年小鼠肌肉质量增加1.17倍，肌肉萎缩标志物减少2.4 - 4.9倍，线粒体生物发生和抗氧化酶表达增加近2 - 3倍。在C2C12细胞中，MEF2A刺激了增殖（edu阳性细胞比载体组增加1.8倍）和分化（分化标记物比载体组增加2至3倍），同时通过OxPhos复合物蛋白和线粒体生物发生基因比载体对照增加1.5至2倍来改善线粒体功能。在机制上，MEF2A直接激活了PGC-1α/NRF2轴，通过ChIP和报告基因实验证实了这一点。救援实验进一步验证了该通路在mef2a介导作用中的关键作用。这些发现表明，MEF2A通过激活PGC-1α/NRF2信号轴，改善线粒体功能和促进肌肉再生，从而减轻肌肉减少症。MEF2A代表了对抗年龄相关性肌肉变性的一个有希望的治疗靶点。

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引用次数: 0

Head organizer: Cerberus and IGF cooperate in brain induction in Xenopus embryos Head organizer：Cerberus和IGF在爪蟾胚胎大脑诱导过程中的合作

IF 2 4区生物学 Q4 Biochemistry, Genetics and Molecular Biology

Cells and Development

Pub Date : 2025-12-01 DOI: 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.

一个世纪前，斯佩曼（Spemann）和曼戈尔德（Mangold）通过两栖动物的组织器移植发现了细胞-细胞信号的神经诱导。斯佩曼后来发现，早期背侧胚泡唇诱导头部，晚期组织者诱导躯干-尾部结构。识别区域特异性组织者信号一直是动物生物学进步的推动力。在没有躯干的情况下诱导出头部被称为拱脑分化。两种特异性头部诱导因子 Cerberus 和胰岛素样生长因子 (Insulin-like growth factors, IGFs)，可诱导头状脑分化，但不诱导躯干-尾部结构。然而，迄今为止，这两种信号是否相互影响尚未研究，这也是本次调查的目的。研究发现，Cerberus（一种抑制 Nodal、BMP 和 Wnt 信号的多价生长因子拮抗剂）与 IGF2（一种通过酪氨酸激酶 IGF 受体提供积极信号、激活 MAPK 和其他通路的生长因子）之间存在密切的合作关系。由 Cerberus 和 IGF2 共同诱导的异位拱脑结构比单独使用其中一种的频率更高、更大。它们包含大脑、环状眼和多个嗅胎座，但没有脊索或体节等躯干结构的痕迹。显性阴性分泌型 IGF 受体 1 阻断了 Cerberus 的活动，表明异位脑的形成需要内源性 IGF 信号。在一个去除了β-catenin的敏化胚胎系统中，IGF2本身并不能诱导神经组织的形成，而与Cerberus结合则能大大促进表达前部标记Otx2和Rx2a的环状脑结构的形成，但不能诱导脊髓或脊索标记的形成。这项工作的主要结论是，IGF 提供了一种最初在整个胚胎中均匀表达的积极信号，这种信号增强了由 Cerberus 介导的组织者特异性消极信号的效果。本文结合神经诱导的历史对这一结果进行了讨论。

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引用次数: 0

Towards an integrated view and understanding of embryonic signalling during murine gastrulation 对小鼠原肠胚形成过程中胚胎信号传导的综合认识和理解。

IF 2 4区生物学 Q4 Biochemistry, Genetics and Molecular Biology

Cells and Development

Pub Date : 2025-12-01 DOI: 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.

在哺乳动物原肠胚形成开始时，属于Bmp、Wnt、Nodal和Fgf信号通路的分泌信号分子诱导并形成原始条纹，标志着产生身体计划的细胞重排的开始。我们目前对信号如何在三维空间中指定和组织胚层的理解，主要来自于几十年来对小鼠胚胎进行的基因实验。然而，事件的确切时空序列仍然知之甚少，这既是因为缺乏可用于实时可视化信号和分化的可处理模型，也是因为这些早期发育事件的分子和细胞复杂性。近年来，一波新的体外胚胎模型开始揭示原始条纹形成过程中的信号动力学。在这里，我们从信号传导的角度讨论了广泛采用的小鼠胚胎模型（称为类胃原肠）与真实胚胎之间的异同。我们将重点关注信号通路相互作用的基因调控网络，并概述未来的一些挑战。最后，我们提供了一个关于胚胎模型如何通过计算建模来推进我们对信号动力学的理解的观点。

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引用次数: 0

Comments on the Hox timer and related issues 关于Hox定时器和相关问题的评论。

IF 2 4区生物学 Q4 Biochemistry, Genetics and Molecular Biology

Cells and Development

Pub Date : 2025-12-01 DOI: 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.

2024年不仅是Hilde Pröscholdt-Mangold和Hans Spemann发现组织者的100周年，也是发现同源盒的40周年，同源盒是一个DNA区域，编码DNA结合肽，存在于几个对原肠胚至关重要的转录因子中。特别是，这个序列在羊膜Hox基因家族的39个成员中被发现，这一系列基因在原肠胚形成中期被激活，并参与沿延伸的前后体轴组织形态。在过去的30 年里，对它们在各种情况下的协调调节的研究逐渐揭示了它们令人惊讶的调节策略，这些策略基于顺式作用的机制，可以将沿着染色质纤维的一系列基因的线性分布转化为沿着我们的各种身体轴观察到的适当的形态序列。第一个调控层是由Hox计时器控制的，这是一种实现这些基因按照染色体顺序按时间顺序激活的机制。在这里，我们讨论这个机制的各个方面，强调它的一些奇异之处。

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引用次数: 0

The evolutionary origin and mechanism of chordate tail regeneration. An ancient tale? 脊索动物尾巴再生的进化起源与机制。一个古老的传说？

IF 2 4区生物学 Q4 Biochemistry, Genetics and Molecular Biology

Cells and Development

Pub Date : 2025-12-01 DOI: 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.

脊索动物尾巴再生代表了一些脊索动物能够部分或完全再生其主要轴的显著部分的能力。在这篇综述中，我们将讨论脊索动物的再生能力，已知的有助于再生尾巴的细胞来源，脊髓和脊柱等各种结构是如何重建的，以及再生尾巴的尺度是如何调节的。最后，我们提出尾巴再生是进化保守的，与尾巴发育有着根本的不同，但这一过程的起源和机制尚不清楚。

引用次数: 0

Self-organization from organs to embryoids by activin in early amphibian development 早期两栖动物发育过程中器官到胚状体的自组织。

IF 2 4区生物学 Q4 Biochemistry, Genetics and Molecular Biology

Cells and Development

Pub Date : 2025-12-01 DOI: 10.1016/j.cdev.2025.203996

Makoto Asashima , Yumeko Satou-Kobayashi , Yoshikazu Haramoto , Takashi Ariizumi

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.

胚胎发育是一个复杂的自组织过程，由一系列分子和细胞水平的调控事件精心策划，最终形成一个功能齐全的生物体。本文就激活蛋白作为中胚层诱导因子及其自组织特性作一综述。激活素在未受精卵和胚胎中都被检测到，这表明它参与了早期发育过程。为了探索其作用，用不同浓度的激活素处理动物帽细胞——来自两栖动物囊胚期胚胎的动物极的多能细胞。结果表明，激活素诱导中胚层组织，包括血液、肌肉和脊索，呈剂量依赖性。激活素与维甲酸共同作用进一步促进了肾脏和胰腺组织的发育，而激活素单独作用则刺激了跳动心脏组织的形成。在随后的实验中，高浓度的激活素赋予动物帽细胞类似组织的活性。预处理时间影响结果：较长的暴露会诱导前结构，如眼睛，而较短的暴露会导致后结构，如尾巴。这些发现反映了适度的自组装，细胞变得越来越有组织。在另一个实验中，激活素被用来制造人工梯度。在这种梯度下培养的外植体发育成具有明确的前后轴、背腹轴和左右轴的胚状体，体现了高阶自组织。这些结果表明，控制激活素梯度可以驱动几乎完整的蝌蚪样幼虫的形成，有效地再现了早期胚胎发生的过程。该系统对轴的形成和器官发生机制提供了有价值的见解，为未来的发育生物学研究提供了一个有希望的平台。

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引用次数: 0

Maternal control of embryonic dorsal organizer in vertebrates 脊椎动物胚胎背器官的母性控制。

IF 2 4区生物学 Q4 Biochemistry, Genetics and Molecular Biology

Cells and Development

Pub Date : 2025-12-01 DOI: 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.

胚胎中身体轴和发育蓝图的建立一直是发育生物学的核心问题，几个世纪以来一直吸引着科学家。1924年，Hans Spemann和Hilde Mangold发现了两栖动物胚胎体轴形成的背侧组织者，这一领域取得了里程碑式的成就。从那时起，大量的研究表明，背侧组织器在脊椎动物中是进化保守的。这个组织者作为一个信号中心，引导相邻细胞走向特定的命运，并协调模式的形成，以建立胚胎轴。在组织者被发现70 年后，对不同模式动物物种的研究表明，在囊胚形成过程中，局部激活的β-catenin信号在组织者诱导中起着不可或缺的作用。然后，努力鉴定β-catenin在囊胚中激活的启动物。现在看来，母体呼鲁瓦是一种跨膜蛋白，至少在硬骨鱼和青蛙中是一种真正的组织者诱导剂，它可以激活下游信号通路，包括但可能不限于β-连环蛋白通路。需要更多的研究来解码控制组织者诱导的完整分子网络。

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引用次数: 0

Cell biology of the chick organizer: Origins, composition, population dynamics and fate 小鸡组织者的细胞生物学：起源，组成，种群动态和命运。

IF 2 4区生物学 Q4 Biochemistry, Genetics and Molecular Biology

Cells and Development

Pub Date : 2025-12-01 DOI: 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.

2024年是发育生物学领域最重要、最具影响力的论文之一——Spemann和Mangold发表报告发现“组织者”（organizer）的100周年 ，该“组织者”可以诱导和塑造神经系统，也可以塑造中胚层的轴-外侧轴。虽然许多论文已经研究了组织者的信号传导方面，但相对较少的论文集中在组织者细胞的细胞生物学上。在这里，我们回顾了超过12年来关于小鸡组织者的知识，包括细胞起源、命运、组成、细胞运动、细胞群体特性和小鸡组织者（原始条纹的尖端）的分子动力学。呈现出来的是一幅极其复杂和动态的细胞群的图景，它们的特性随着时间和空间的变化而变化，这与“教科书”上的观点大不相同，教科书上认为，在正常胚胎的早期发育过程中，一群静止的细胞在被清除之前，会在正常胚胎中发挥特定的功能。其中一些发现也对单细胞RNA测序实验结果的解释具有更普遍的意义。

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引用次数: 0

Wnt and BMP signaling pathways pattern the anterior neuroectoderm of the indirect-developing hemichordate Ptychodera flava Wnt和BMP信号通路模式的前神经外胚层间接发展的半硬掌黄掌。

IF 2 4区生物学 Q4 Biochemistry, Genetics and Molecular Biology

Cells and Development

Pub Date : 2025-12-01 DOI: 10.1016/j.cdev.2025.204060

Yann Le Petillon , Tzu-Pei Fan , Yi-Chih Chen , Yi-Hsien Su

The chordate gastrula organizer establishes Wnt and BMP signaling gradients that are essential for generating the chordate body plan. In non-chordate deuterostomes, including echinoderms and hemichordates, these two signals also contribute to body axial patterning, although it remains debatable whether there is a bona fide equivalent tissue to the organizer. One consequence of these patterning mechanisms is the formation of a neuron population originating from the anterior neuroectoderm (ANE). Wnt signaling is essential for restricting the ANEs in sea urchins with planktonic larval stages as well as direct-developing hemichordates (without larval stages). However, it is difficult to infer the ancestral mechanisms in deuterostomes since information is lacking regarding the mechanisms of ANE formation in indirect-developing hemichordates (with larval stages). Here, we delineate the deployment of Wnt signaling components as well as the roles of Wnt and BMP signals in ANE development in the indirect-developing hemichordate Ptychodera flava. We show that posterior Wnt signaling functions to pattern the anteroposterior axis and restrict the ANE during gastrulation. Meanwhile, BMP signaling promotes ANE development and regeneration during gastrulation, although it initially represses the formation of neural tissues. Our findings thus support a conserved role for Wnt signaling in ANE restriction and suggest a biphasic function of BMP signaling during ANE formation, providing insights into the patterning mechanisms within the common ancestor of deuterostomes.

脊索动物原肠组织器建立了Wnt和BMP信号梯度，这对于脊索动物体计划的产生至关重要。在无脊索动物后口动物中，包括棘皮动物和半脊索动物，这两种信号也有助于身体轴向模式，尽管是否存在与组织者真正等效的组织仍然存在争议。这些模式机制的一个结果是神经元群的形成起源于前神经外胚层（ANE）。Wnt信号对于限制浮游幼体海胆和直接发育的半足海胆（无幼体）的ANEs至关重要。然而，由于缺乏关于间接发育的半足虫（含幼虫期）ANE形成机制的信息，很难推断后口动物的祖先机制。在这里，我们描述了Wnt信号组件的部署，以及Wnt和BMP信号在间接发生的半胆酸类黄斑拟蟹（Ptychodera flava） ANE发展中的作用。我们发现后向Wnt信号在原肠形成过程中对前后轴进行模式化并限制ANE。同时，BMP信号在原肠胚形成过程中促进ANE的发育和再生，尽管它最初抑制神经组织的形成。因此，我们的研究结果支持了Wnt信号在ANE限制中的保守作用，并提出了BMP信号在ANE形成过程中的双相功能，为后口动物共同祖先的模式机制提供了见解。

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引用次数: 0