Cells and Development最新文献_第2页

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

The role of the node in maintaining axial progenitors 淋巴结在维持轴向祖细胞中的作用。

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.2025.204004

Raffee Wright, Valerie Wilson

The production of the vertebrate body axis involves the coordinating activity of the organizer, which coincides in amniotes with the node in the gastrulating embryo. This organizer orchestrates nearby axial progenitor populations that produce the spinal cord and musculoskeleton. Various findings, discussed further in this review, suggest that some of these axial progenitors exhibit stem cell-like properties as they display maintenance behaviour such as self-renewal and sustained contribution to derivative tissues. We consider how the node acts to maintain and regulate these progenitor populations by providing mechanical forces and a niche-like signalling environment.

脊椎动物体轴的产生涉及组织者的协调活动，这在羊膜中与原肠胚的结相吻合。这个组织者协调产生脊髓和肌肉骨骼的轴向祖细胞群。本综述中进一步讨论的各种发现表明，这些轴向祖细胞中的一些表现出干细胞样特性，因为它们表现出诸如自我更新和对衍生组织的持续贡献等维持行为。我们考虑节点如何通过提供机械力和类似生态位的信号环境来维持和调节这些祖细胞群。

引用次数: 0

Dynamic behavior of cell-cell adhesion factors in collective cell migration 细胞-细胞粘附因子在细胞集体迁移中的动态行为。

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.2025.203995

Sayuki Hirano , Kazuhiro Aoki , Naoto Ueno

Collective cell migration is a fundamental process underlying various biological phenomena, including embryonic development and cancer cell invasion. The cohesive yet flexible movement of cell collectives largely depends on the coordinated regulation of cell-cell and cell-substrate adhesions. In this review, we summarize the regulation of key cell-cell junction components, such as cadherins and zonula occludens proteins during collective cell migration, with a particular focus on the recently discovered multifaceted roles of ZO-1 in both cell-cell and cell-substrate interactions.

细胞集体迁移是多种生物现象的基本过程，包括胚胎发育和癌细胞侵袭。细胞集体的内聚而灵活的运动在很大程度上取决于细胞-细胞和细胞-底物粘附的协调调节。在这篇综述中，我们总结了细胞集体迁移过程中关键细胞-细胞连接成分（如钙粘蛋白和闭塞带蛋白）的调控，并特别关注了最近发现的ZO-1在细胞-细胞和细胞-底物相互作用中的多方面作用。

引用次数: 0

Transcending the hegemony of the molecular machine through an organic renewal of biology and biomedicine 通过生物学和生物医学的有机更新，超越分子机器的霸权。

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.2025.204018

Amy E. Shyer, Alan R. Rodrigues

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.

从20世纪到今天，研究生命系统的主要方法是专注于遗传学和生物化学的还原论方法。对基因的寻找和对其生化结果的阐明，已经在研究、教育课程、学术推广和通过奖励分配声望方面组织了资金。这种还原论与机器本体论密切相关。我们将讨论如何把生命看作是由一组分子机器产生的，这是解决生物学关键问题的主要瓶颈。我们将讨论如何超越它并不取决于新技术，而是一种可以被称为“有机”的生命的全新视角。此外，我们认为研究形态如何产生，形态发生，是生物学和生物医学有机更新的关键。尽管形态发生目前被视为发育生物学的一个附属分支，以及亚细胞尺度上分子模式过程的结果，但我们将认为，形态及其在超细胞尺度上的自组织能力是胚胎发育和疾病的基本联系。我们认为，无法从有机超细胞的角度来理解形式，是研究癌症和慢性病流行等健康问题的主要瓶颈。

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引用次数: 0

‘Three signals - three body axes’ as patterning principle in bilaterians 三信号-三体轴 "是两栖动物的模式化原则。

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.2024.203944

Christof Niehrs , Ettore Zapparoli , Hyeyoon Lee

In vertebrates, the three orthogonal body axes, anteroposterior (AP), dorsoventral (DV) and left-right (LR) are determined at gastrula and neurula stages by the Spemann-Mangold organizer and its equivalents. A common feature of AP and DV axis formation is that an evolutionary conserved interplay between growth factors (Wnt, BMP) and their extracellular antagonists (e.g. Dkk1, Chordin) creates signaling gradients for axial patterning. Recent work showed that LR patterning in Xenopus follows the same principle, with R-spondin 2 (Rspo2) as an extracellular FGF antagonist, which creates a signaling gradient that determines the LR vector. That a triad of anti-FGF, anti-BMP, and anti-Wnt governs LR, DV, and AP axis formation reveals a unifying principle in animal development. We discuss how cross-talk between these three signals confers integrated AP-DV-LR body axis patterning underlying developmental robustness, size scaling, and harmonious regulation. We propose that Urbilateria featured three orthogonal body axes that were governed by a Cartesian coordinate system of orthogonal Wnt/AP, BMP/DV, and FGF/LR signaling gradients.

在脊椎动物中，三个正交体轴，即前后轴（AP）、背腹轴（DV）和左右轴（LR），是在胚胎期和神经细胞期由 Spemann-Mangold 组织器及其等同物决定的。AP轴和DV轴形成的一个共同特征是，生长因子（Wnt、BMP）和它们的细胞外拮抗剂（如Dkk1、Chordin）之间在进化过程中形成的相互作用为轴形态的形成创造了信号梯度。最近的研究表明，爪蟾的 LR 形态也遵循同样的原理，R-spondin 2（Rspo2）是细胞外 FGF 拮抗剂，它产生的信号梯度决定了 LR 的矢量。抗 FGF、抗 BMP 和抗 Wnt 三者共同控制着 LR、DV 和 AP 轴的形成，这揭示了动物发育中的一个统一原则。我们讨论了这三种信号之间的交叉作用是如何赋予AP-DV-LR体轴综合模式化的，这种模式化是发育稳健性、大小缩放和和谐调控的基础。我们提出 Urbilateria 具有三个正交的体轴，这些体轴受正交的 Wnt/AP、BMP/DV 和 FGF/LR 信号梯度的直角坐标系控制。

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引用次数: 0

Functional attributes of the anterior mesendoderm in patterning the anterior neural structures during head formation in the mouse 小鼠头部形成过程中前中胚层在前神经结构中的功能属性。

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.2025.203999

Patrick P.L. Tam, Pragathi Masamsetti

Induction of the neural ectoderm and the patterning of embryonic brain are the requisite organizing activity for head formation. Studies of loss-of-function mouse mutants that displayed a head truncation phenotype pointed to a key functional role of the anterior mesendoderm in anterior neural patterning. In this overview, we highlight the learning of the molecular attributes underpinning the formation of the anterior mesendoderm, the acquisition of ectoderm competence in the epiblast and the patterning of the embryonic brain during gastrulation and neurulation.

神经外胚层的诱导和胚胎脑的形成是头形成的必要组织活动。对显示头部截断表型的功能丧失小鼠突变体的研究指出，前中胚层在前神经模式中起着关键的功能作用。在这篇综述中，我们强调了支持前中胚层形成的分子属性的学习，外胚层能力在外胚层的获得以及胚胎脑在原肠胚形成和神经发育期间的模式。

引用次数: 0

A modular organization of mammalian gastrulation and the Spemann-Mangold organizer 哺乳动物原肠胚的模块化组织和Spemann-Mangold组织者。

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.2025.204031

Alfonso Martinez Arias , André Dias , Alexandra E. Wehmeyer , Sebastian J. Arnold , Ulla-Maj Fiúza

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.

对两栖动物胚胎的研究揭示了细胞群的存在，组织者在制定身体计划方面起着核心作用。一个是Spemann-Mangold组织者（SMO），它与神经系统的诱导和头部的发育有关，而另一个则与躯干和尾巴的发育有关。在其他脊椎动物中也发现了这些组织者的同源物。在小鼠中，SMO组织者与中早期原肠的一个区域有关，尾干组织者与淋巴结有关。总之，这些观察表明，脊椎动物身体的模块化组织计划分为三个领域。一个是最前面的，能够形成大脑；一个是中间的，与神经诱导和头部有关；另一个致力于轴向伸展。对哺乳动物发育的多能干细胞模型类原肠细胞的研究表明，这些模块是独立的发育单元。在这里，我们讨论了类胃原体的发现与胚胎组织者活动的关系，以及这种模块化组织对脊椎动物身体计划进化的影响。

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引用次数: 0

Temporal regulation of endoderm convergence and extension by the BMP activity gradient through mesoderm-dependent and independent mechanisms BMP活性梯度通过中胚层依赖和独立机制对内胚层收敛和延伸的时间调控。

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.2025.204021

Chia-Teng Chang, Tony Tsai, Lila Solnica-Krezel

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.

一百年前，Spemann和Mangold发现了组织者，这是一个关键的胚胎区域，通过指导细胞的命运和形态发生来建立脊椎动物的身体轴。一个保守的脊椎动物机制涉及到在原肠形成过程中由组织者表达的分子对腹侧到背侧BMP活性梯度的调节。在斑马鱼中，BMP信号通过抑制平面细胞极性（PCP）信号和调节细胞粘附来控制中胚层细胞的收敛和延伸（C&E）。这使得侧侧细胞向背中线聚集，同时引导腹侧细胞向尾芽聚集。然而，BMP在内胚层运动中的作用及其调控功能的时间精度仍然知之甚少。利用光遗传学和其他功能丧失和功能获得的方法，我们研究了BMP在中胚层和内胚层C&E中的作用。我们发现低BMP信号传导促进两个胚层的扩展，而高BMP信号传导抑制它们的C&E。值得注意的是，1 h的BMP信号激活迅速地将中胚层和内胚层细胞的背向腹侧迁移重新定向。然而，当BMP信号在BMP信号减少的胚胎的内胚层中选择性地升高时，内胚层仍然模仿中胚层的运动，这表明内胚层对BMP的反应是非细胞自主的。我们发现，BMP信号正常或升高的原胚中内胚层细胞的运动并不完全依赖于中胚层或Cxcl12b/Cxcr4a GPCR途径，这表明内胚层C&E背后有其他机制。我们的研究结果强调了BMP形态原梯度在中胚层和内胚层细胞协调的C&E运动中的关键作用。BMP采用直接和间接两种机制来确保强健的胚胎模式和胚层的形态发生。

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引用次数: 0

Tissue mechanics modulate morphogen signalling to induce the head organiser 组织力学调节形态因子信号诱导头部组织者。

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.2024.203984

Matyas Bubna-Litic , Guillaume Charras , Roberto Mayor

Morphogenetic movements and specification of germ layers during gastrulation are key processes that establish the vertebrate body plan. Despite substantial research into the role of tissue mechanics during gastrulation and detailed characterisation of the molecular signalling networks controlling fate determination, the interplay of mechanical cues and biochemical signals during fate specification is poorly understood. Morphogens that activate Activin/Nodal/Smad2 signalling play a key role in mesoderm induction and axial patterning. We investigate the interplay between a single molecular input and a mechanical input using the well-established ex vivo system of Activin-induced explants of the mid-blastula X. laevis animal cap ectoderm. Activin alone induces mesoderm to form a complex elongating tissue with axial patterning, making this system similar to gastruloids generated in other model organisms. We observed an increase in the expression of dorsal mesoderm markers, such as chordin and goosecoid, and loss of elongation, in Activin-induced explants that were mechanically stimulated through uniaxial compression during the induction period. In addition, head mesoderm specific markers, including cerberus 1, were also increased. We show that mechanical stimulation leads to an increase in nuclear β-catenin activity. Activation of β-catenin signalling is sufficient to induce head Organiser gene expression. Furthermore, inhibition of β-catenin is sufficient to rescue the effect of compression on an early Wnt-signalling response gene siamois. Taken together these observations support the role of mechanical stimulation in modulating Activin-dependent mesoderm induction in favour of head Organiser formation. Given the conserved role of β-catenin in the dorsal specification and the dynamic morphogenetic movements of dorsal gastrula regions, mechanics-dependent Organiser induction may be found in other vertebrate species. Finally, the finding that mechanical cues affect β-catenin-dependent axial specification can be applied in the future development of more biologically relevant and robust synthetic organoid systems.

原肠胚形成过程中胚层的形态运动和发育是确定脊椎动物体表的关键过程。尽管对组织力学在原肠形成过程中的作用和控制命运决定的分子信号网络的详细特征进行了大量研究，但在命运规范过程中，机械线索和生化信号的相互作用知之甚少。激活Activin/Nodal/Smad2信号传导的形态因子在中胚层诱导和轴向模式中起关键作用。我们利用激活素诱导的中囊胚X. laevis动物帽外胚层外植体的体外系统，研究了单分子输入和机械输入之间的相互作用。激活素单独诱导中胚层形成具有轴向图案的复杂细长组织，使该系统类似于其他模式生物中产生的原肠样细胞。我们观察到，激活素诱导的外植体在诱导期通过单轴压缩机械刺激时，背中胚层标记物（如弦蛋白和goosecoid）的表达增加，伸长减少。此外，头中胚层特异性标记（包括cerberus 1）也有所增加。我们发现机械刺激导致核β-连环蛋白活性增加。β-连环蛋白信号的激活足以诱导头部组织者基因的表达。此外，抑制β-catenin足以挽救对早期wnt信号反应基因siamois的压迫作用。综上所述，这些观察结果支持机械刺激在调节激活素依赖的中胚层诱导中有利于头部组织者形成的作用。鉴于β-catenin在背部规范和背部原肠区动态形态发生运动中的保守作用，可能在其他脊椎动物物种中发现机械依赖的组织者诱导。最后，机械线索影响β-连环蛋白依赖轴向规范的发现可以应用于未来开发更具生物学相关性和健壮性的合成类器官系统。

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引用次数: 0

Mucociliary cell type compositions - bridging the gap between genes and emergent tissue functions 粘液纤毛细胞类型组成-弥合基因和紧急组织功能之间的差距。

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.2025.204019

Peter Walentek

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.

当多种细胞类型聚集在一起形成一个组织特异性集体时，细胞功能和细胞间相互作用的结合导致了新的行为和特性，而不仅仅是单个特征的简单添加，通常被称为突发性组织功能。在进化过程中，器官的功能适应受到细胞类型组成变化的显著影响，在疾病中，细胞类型组成的畸变导致器官功能受损。研究调节细胞类型组成的机制可以阐明一个重要的组织元水平，它连接基因功能和细胞特征，促进集体细胞行为和新组织功能的出现。由于其独特的进化定位和多样的功能，粘液纤毛上皮可以提供一个最佳系统来揭示细胞类型组成的适应原理机制，促进新的或优化现有组织功能的进化，并可能揭示对抗人类疾病的新切入点。通过对具有不同特化细胞和细胞类型组成的粘膜纤毛组织的信号传导、转录、表观遗传和形态发生机制的综合研究，可以帮助我们将基因功能与细胞集体中决定紧急组织功能的自组织行为联系起来。沿着这条路线向前发展，有可能揭示粘膜纤毛自组织的新原理，并揭示跨物种和器官系统产生和修改紧急组织功能的广泛适用原理。

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引用次数: 0