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Dynamics of primary cilia in endothelial and mesenchymal cells throughout mouse lung development 内皮细胞和间充质细胞中原代纤毛在小鼠肺发育过程中的动态。
IF 1.5 3区 生物学 Q2 ANATOMY & MORPHOLOGY Pub Date : 2025-03-08 DOI: 10.1002/dvdy.70008
Stephen Spurgin, Ange Michelle Nguimtsop, Fatima N. Chaudhry, Sylvia N. Michki, Jocelynda Salvador, M. Luisa Iruela-Arispe, Jarod A. Zepp, Saikat Mukhopadhyay, Ondine Cleaver

Cilia are specialized structures found on a variety of mammalian cells, with variable roles in the transduction of mechanical and biological signals (by primary cilia, PC), as well as in the generation of fluid flow (by motile cilia). Their critical role in the establishment of a left–right axis in early development is well described, as well as in the defense immune function of multiciliated upper airway epithelium. By contrast, detailed analysis of the ciliary status of specific cell types during organogenesis and postnatal development has received less attention. In this study, we investigate the progression of ciliary status within the endothelium and mesenchyme of the lung. Remarkably, we find that pulmonary endothelial cells (ECs) lack PC at all stages of development, except in low numbers in the proximal portions of older pulmonary arteries. Mesenchymal cells, by contrast, widely exhibit PC in early development, and a large subset of PDGFRα+ fibroblasts maintain PC into adulthood. The dynamic and differential ciliation of multiple cellular populations in the developing lung both challenges prior assertions that PC are found on all cells and highlights a need to understand their spatiotemporal functions.

纤毛是在多种哺乳动物细胞中发现的特殊结构,在机械和生物信号的转导(通过初级纤毛,PC)以及流体流动的产生(通过活动纤毛)中发挥着不同的作用。它们在早期发育中左右轴的建立以及多纤毛上气道上皮的防御免疫功能中的关键作用已被很好地描述。相比之下,在器官发生和出生后发育过程中,对特定细胞类型纤毛状态的详细分析却很少受到关注。在这项研究中,我们研究了纤毛状态在肺内皮和间质中的进展。值得注意的是,我们发现肺内皮细胞(ECs)在所有发育阶段都缺乏PC,除了在较老的肺动脉近端部分数量较少。相比之下,间充质细胞在早期发育中广泛表现出PC,而PDGFRα+成纤维细胞的很大一部分在成年期仍保持PC。肺发育过程中多个细胞群的动态和差异调节都挑战了先前关于所有细胞都存在PC的断言,并强调了了解其时空功能的必要性。
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引用次数: 0
Human stem cell model of neural crest cell differentiation reveals a requirement of SF3B4 in survival, maintenance, and differentiation 神经嵴细胞分化的人干细胞模型揭示了SF3B4在生存、维持和分化中的需要。
IF 1.5 3区 生物学 Q2 ANATOMY & MORPHOLOGY Pub Date : 2025-03-06 DOI: 10.1002/dvdy.70009
Casey Griffin, Jean-Pierre Saint-Jeannet

Background

In vitro modeling is a powerful approach to investigate the pathomechanisms driving human congenital conditions. Here, we use human embryonic stem cells (hESCs) to model Nager and Rodriguez syndromes, two craniofacial conditions characterized by hypoplastic neural crest-derived craniofacial bones, caused by pathogenic variants of SF3B4, a core component of the spliceosome.

Results

We observed that siRNA-mediated knockdown of SF3B4 interferes with the production of hESC-derived neural crest cells, as seen by a marked reduction in neural crest gene expression. This phenotype is associated with an increase in neural crest cell apoptosis and premature neuronal differentiation.

Conclusions

Altogether, these results point to a role of SF3B4 in neural crest cell survival, maintenance, and differentiation. We propose that the dysregulation of these processes may contribute to Nager/Rodriguez syndrome-associated craniofacial defects.

背景:体外建模是研究人类先天性疾病病理机制的有力方法。在这里,我们使用人类胚胎干细胞(hESCs)来模拟纳格综合征和罗德里格斯综合征,这两种颅面疾病的特点是神经嵴衍生颅面骨骼发育不良,由剪接体的核心成分SF3B4的致病变体引起:我们观察到,siRNA 介导的 SF3B4 基因敲除会干扰 hESC 衍生神经嵴细胞的生成,表现为神经嵴基因表达明显减少。这种表型与神经嵴细胞凋亡增加和神经元过早分化有关:总之,这些结果表明了 SF3B4 在神经嵴细胞存活、维持和分化中的作用。我们认为,这些过程的失调可能是导致纳格/罗德里格斯综合征相关颅面缺陷的原因之一。
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引用次数: 0
Editorial highlights 社论强调
IF 1.5 3区 生物学 Q2 ANATOMY & MORPHOLOGY Pub Date : 2025-03-04 DOI: 10.1002/dvdy.70007
Paul A. Trainor
<p>Every organism is a model organism for understanding development, evolution, disease, and regeneration, and we have only begun to scratch the surface of the interdisciplinary genetic, molecular, cellular, and developmental mechanisms that regulate these biological processes. These “highlights” denote exciting advances recently reported in <i>Developmental Dynamics</i> that illustrate the complex dynamics of developmental biology.</p><p><b>Regeneration</b> “Functional significance of earthworm clitellum in regulating the various biological aspects of cell survival and regeneration” by Jackson Durairaj Selvan Christyraj, Ashwin Barath Vaidhyalingham, Chandini Sengupta, Kamarajan Rajagopalan, Kayalvizhi Vadivelu, Nandha Kumar Suresh, and Bharathi Venkatachalam <i>Dev Dyn</i> 254.3, pp. 212–221, https://doi.org/10.1002/dvdy.751. Earthworms exhibit a remarkable ability to rapidly heal and completely regenerate within a short period of time. Earthworms are therefore an ideal model for studying the mechanisms that regulate stem cell biology and regeneration. Over 7000 different species of earthworms have been identified and described, and this review describes new insights into the functions of the clitellum, which is a glandular structure that sits near the head. During epimorphosis, undifferentiated stem cells that reside in the clitellar region divide and form a blastema, which then develops into new tissue. In contrast, during morphallaxis, in which regeneration occurs without the formation of a blastema, it is thought that cells in the clitellum undergo trans-differentiation. Either way, the clitellum is regarded as a stem cell reservoir that regulates regeneration. However, in addition to regeneration, the clitellum plays essential roles in reproduction, organogenesis, and aging.</p><p><b>Cardiovascular Biology</b> “Modulation of mechanosensitive genes during embryonic aortic arch development” by Hummaira Banu Siddiqui, Tansu Golcez, Merve Çelik, Börteçine Sevgin, Mervenur Çoban, İlke Süder, Özen Kaya, Nesrin Özören, and Kerem Pekkan <i>Dev Dyn</i> 254.3, pp. 222–239, https://doi.org/10.1002/dvdy.728. The embryonic aortic arches are dynamic vascular structures that develop into the great arteries of the cardiovascular system. The extracellular matrix is known to play important roles in aortic arch and vascular morphogenesis, and computational and other types of modeling have linked mechanical properties such as blood pressure, wall shear stress, outflow tract orientation, and blood flow, to the developmental morphology of the aortic arches. Developmental malformations of the aortic arches manifest as congenital heart defects. In this study, the authors modulated the activity of genes associated with wall shear stress such as TGFβ3 and MMP2. TGFβ3 knockdown results in decreases in collagen and elastin density, with corresponding alterations in hemodynamics and blood pressure, that lead to detrimental effects on lumen diameter and the accumulatio
每一种生物都是理解发育、进化、疾病和再生的模式生物,而我们才刚刚开始触及调节这些生物过程的跨学科遗传、分子、细胞和发育机制的表面。这些“亮点”表示最近在《发育动力学》上报道的令人兴奋的进展,这些进展说明了发育生物学的复杂动力学。《蚯蚓阴蒂在调节细胞存活和再生的各种生物学方面的功能意义》,作者:Jackson Durairaj Selvan christraj, Ashwin Barath Vaidhyalingham, Chandini Sengupta, Kamarajan Rajagopalan, Kayalvizhi Vadivelu, Nandha Kumar Suresh和Bharathi Venkatachalam Dev Dyn 254.3, pp. 212-221, https://doi.org/10.1002/dvdy.751。蚯蚓表现出一种非凡的能力,可以在短时间内迅速愈合并完全再生。因此,蚯蚓是研究调节干细胞生物学和再生机制的理想模型。超过7000种不同种类的蚯蚓已经被识别和描述,这篇综述描述了对阴蒂功能的新见解,这是一个位于头部附近的腺体结构。在表皮形成过程中,位于阴蒂区的未分化干细胞分裂并形成囊胚,囊胚随后发育成新组织。相反,在形态轴(morphallaxis)过程中,再生发生在没有形成胚芽的情况下,人们认为阴蒂中的细胞经历了反分化。不管怎样,阴蒂被认为是调节再生的干细胞储存库。然而,除了再生之外,阴蒂在生殖、器官发生和衰老中起着至关重要的作用。心血管生物学“机械敏感基因在胚胎主动脉弓发育中的调节”,Hummaira Banu Siddiqui, Tansu Golcez, Merve Çelik, Börteçine Sevgin, Mervenur Çoban, İlke s<e:2> der, Özen Kaya, Nesrin Özören, and Kerem Pekkan Dev Dyn 254.3, pp 222-239, https://doi.org/10.1002/dvdy.728。胚胎的主动脉弓是动态的血管结构,发育成心血管系统的大动脉。众所周知,细胞外基质在主动脉弓和血管形态发生中起着重要作用,计算和其他类型的建模将血压、管壁剪切应力、流出道方向和血流等力学特性与主动脉弓的发育形态联系起来。主动脉弓发育畸形表现为先天性心脏缺陷。在这项研究中,作者调节了与壁剪切应力相关的基因,如tgf - β3和MMP2的活性。tgf - β3敲低导致胶原蛋白和弹性蛋白密度降低,血流动力学和血压随之改变,从而对管腔直径和血细胞积累产生不利影响。敲低MMP2可显著增加COL-III表达和主动脉弓直径,从而影响组织重塑、心垫细胞迁移和血管成熟。这两种主要机械敏感网络的扰动支持了心脏基因调控在心血管发育过程中受到机械控制的观点。《包括Zfhx4在内的基因在小鼠和斑马鱼中的表达分析揭示了颅面发育的时空保守分子基础》,作者:刘树杰、徐林、岛真诚、鸣美丽香、高畑义文、中村丽子、涉谷广、田村雅鲁、志田由纪、犬武Toshihiro、Nukada Yuko、宫泽正明、畑健二、西村丽子、山城隆、田崎淳一和黑坂广,Dev Dyn 254.3, pp. 257-271。https://doi.org/10.1002/dvdy.740。小鼠和斑马鱼经常被用来模拟人类疾病,如先天性颅面缺陷,包括口面裂。尽管斑马鱼的腭发育在形态上与哺乳动物不同,但神经嵴细胞在这两个物种的腭发育过程中都起着重要的作用,它们的发育依赖于共同的或保守的分子网络。在这项研究中,作者首先关注Sox9,并鉴定出86个基因在小鼠和斑马鱼中表现出相似的表达动态。然后,他们重点研究了Zfhx4/ Zfhx4及其在颅面发育过程中的表达和功能,特别是在上颌。Zfhx4/ Zfhx4的扰动分别导致小鼠腭架发育破坏和斑马鱼筛板畸变。斑马鱼的筛板被认为相当于哺乳动物的初级上颚,zfhx4似乎是斑马鱼神经嵴细胞迁移和面部原基形成所必需的。 这些结果为斑马鱼和小鼠颅面发育的相似性提供了进一步的证据,并为人类的颅面裂缝提供了新的线索,其中一些最近与人类同源基因ZFHX4的致病变异有关。因此,阐明不同疾病模型之间颅面发育的共同机制对于理解个体物种表型的潜在机制至关重要。一项伴随研究探讨了颅面疾病发病机制中的基因-环境相互作用。“foxe1突变斑马鱼表现出甲状腺功能低下的表型和颅面畸形对乙醇的敏感性增加”,作者:Sophie Raterman, Frank Wagener, Jan Zethof, Vincent Cuijpers, Peter Klaren, Juriaan Metz和Johannes Von den Hoff Dev Dyn 254.3, pp. 240-256, https://doi.org/10.1002/dvdy.745。大多数出生缺陷被认为是多因素的起源,孟德尔疾病的不完全外显是相当普遍的,可能是由于不完全外显,可变的表达性,甚至基因-环境相互作用都可能导致基因型和表型之间的不一致。众所周知,怀孕期间吸毒、吸烟和饮酒等环境因素会增加先天性畸形的风险。FOXE1是一种对正常腭形成和甲状腺形态发生很重要的转录因子,人类FOXE1的变异导致Bamforth-Lazarus综合征。本研究探讨了乙醇暴露对foxe1突变斑马鱼颅面畸形风险的影响,该突变斑马鱼颅面畸形可用于Bamforth-Lazarus综合征模型。事实上,暴露于乙醇中的foxe1突变体表现出更高的发育畸形发生率,这表明foxe1与乙醇之间存在明显的相互作用。这种方法现在可以用于进一步研究FOXE1在甲状腺发育和腭发育中的作用,以筛选颅面畸形病因中可能的基因-环境相互作用。Joshua Moore, Rodrigo Moreno-Campos, Arielle Noah, Eileen Singleton和Rosa Uribe Dev Dyn 254.3, pp. 272-287, https://doi.org/10.1002/dvdy.737,“BMP信号通路成员表达在肠神经祖细胞中丰富,是斑马鱼肠神经系统发育所必需的”。肠神经系统是自主神经系统的主要组成部分,控制胃肠道的内在功能。肠神经系统通常被称为“第二大脑”,由数亿个神经元组成,这些神经元以称为神经节的功能单位排列。肠道神经系统主要来源于神经嵴细胞,这些细胞在神经管中出生,然后迁移到原始肠管中,通过增殖、迁移和分化之间的平衡,它们遍布整个胃肠道。本研究探讨调节肠道神经系统和胃肠发育和功能的内在和外在因素。通过转录组学、基因表达、免疫组织化学分析和化学衰减,作者确定了骨形态发生蛋白(BMP)在维持phox2bb+肠道祖细胞数量或祖细胞池分化时间方面的时间依赖性作用。更具体地说,BMP5被证明对胃肠道的定植至关重要,因为在缺乏它的情况下,phox2bb+肠道祖细胞的数量大大减少。神经嵴细胞增殖、迁移或分化受损可导致胃肠道发育障碍,如巨结肠病。
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引用次数: 0
The synergistic link between sonic hedgehog signaling pathway and gut–lung axis: Its influential role toward chronic obstructive pulmonary disease progression 超音刺猬信号通路与肠-肺轴的协同联系:对慢性阻塞性肺疾病进展的影响
IF 1.5 3区 生物学 Q2 ANATOMY & MORPHOLOGY Pub Date : 2025-03-03 DOI: 10.1002/dvdy.70006
Nidhi Mahajan, Vishal Chopra, Kranti Garg, Siddharth Sharma

Sonic Hedgehog (SHH) is an evolutionarily conserved signaling pathway essential for embryonic development, tissue homeostasis, and tumorigenesis. Aberrant activation of the SHH pathway induces various types of cancer and different types of immune dysregulation. SHH is an extremely important morphogen during lung development, as it regulates the interaction between epithelial and mesenchymal transitions (EMT) in the airways. Cigarette smoking triggers the EMT and activates the SHH signaling pathway, which leads to lung damage and the development of various lung diseases, such as COPD, a smoker's disease. SHH also directs the gut–lung axis (GLA) formation via epithelial–mesenchymal signaling. The abruption or alteration of GLA formation is also responsible for COPD pathogenesis. In this review, we elucidate an overview of the SHH pathway and its inhibitor HHIP, SHH's prominence during lung development, and the dysregulation of the SHH signaling pathway in COPD pathogenesis and its link with COPD clinical features. We also provide insights into the SHH pathway linked with the nicotine pathway and gut–lung axis and their influence on COPD pathogenesis.

Sonic Hedgehog (SHH)是一种进化保守的信号通路,对胚胎发育、组织稳态和肿瘤发生至关重要。SHH通路的异常激活诱导各种类型的癌症和不同类型的免疫失调。SHH在肺发育过程中是一个非常重要的形态因子,因为它调节气道上皮和间充质转化(EMT)之间的相互作用。吸烟会触发EMT并激活SHH信号通路,从而导致肺损伤和各种肺部疾病的发展,如COPD(一种吸烟者的疾病)。SHH还通过上皮-间质信号传导指导肠-肺轴(GLA)的形成。GLA形成的破裂或改变也是COPD发病的原因之一。在这篇综述中,我们概述了SHH通路及其抑制剂hip, SHH在肺发育中的突出作用,以及SHH信号通路失调在COPD发病机制中的作用及其与COPD临床特征的联系。我们还提供了与尼古丁通路和肠-肺轴相关的SHH通路及其对COPD发病机制的影响的见解。
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引用次数: 0
Gastric hypoplasia in mice lacking fibroblast growth factor 9 缺乏成纤维细胞生长因子9的小鼠胃发育不全。
IF 1.5 3区 生物学 Q2 ANATOMY & MORPHOLOGY Pub Date : 2025-03-01 DOI: 10.1002/dvdy.70000
Jason C. Mills, Nattapon Thanintorn, Yongjun Yin, Helen McNeill, David M. Ornitz, Spencer G. Willet

Background

Fibroblast Growth Factor 9 (Fgf9) and its paralog Fgf20 are expressed in the developing stomach. We investigate the role of these growth factors during gastric development, using combinations of null alleles.

Results

Analysis of expression databases showed that Fgf9 is expressed in gastric endoderm and surrounding mesoderm such as the mesothelium as early as E8.5, and Fgf20 is expressed in the gastric progenitors of the glandular stomach. To explore whether Fgf9 and Fgf20 are important for gastric development, we examined embryonic stomachs from Fgf9 and Fgf20 null (Fgf9LacZ/LacZ and Fgf20Cre.GFP/Cre.GFP) mice during development. At E18.5, Fgf9LacZ/LacZ stomachs were hypoplastic, lacking the squamous forestomach. No changes to glandular stomach differentiation were observed using representative markers of glandular lineages. Fgf9LacZ/LacZ stomachs were smaller during early development (E12.5 and E15.5). RNA-seq analysis of Fgf9LacZ/LacZ mice at E15.5 showed that squamous-epithelium-associated transcripts were underrepresented, and glandular epithelial transcripts were overrepresented. Analysis of gastric patterning at E12.5 revealed loss of early squamous progenitors in the epithelium, characterized by loss of SOX2+; GATA4 cells. We further show that loss of Fgf20 does not alone impact gastric development nor modify the Fgf9LacZ/LacZ phenotype.

Conclusions

Fgf9 drives gastric growth and squamous epithelial identity during gastric development.

背景:成纤维细胞生长因子9 (Fgf9)及其平行体Fgf20在发育中的胃中表达。我们利用零等位基因的组合来研究这些生长因子在胃发育过程中的作用。结果:表达数据库分析显示,Fgf9早在E8.5时就在胃内胚层及周围中胚层如间皮中表达,Fgf20在腺胃的胃祖细胞中表达。为了探究Fgf9和Fgf20是否在胃发育中起重要作用,我们检测了Fgf9和Fgf20 null (Fgf9LacZ/LacZ和Fgf20Cre.GFP/Cre.GFP)小鼠发育期间的胚胎胃。E18.5时,Fgf9LacZ/LacZ胃发育不全,缺少鳞状前胃。使用腺系的代表性标记未观察到腺胃分化的变化。Fgf9LacZ/LacZ在发育早期(E12.5和E15.5)胃较小。Fgf9LacZ/LacZ小鼠在E15.5时的RNA-seq分析显示,鳞状上皮相关转录物的代表性不足,而腺上皮转录物的代表性过高。E12.5的胃图分析显示上皮中早期鳞状祖细胞的缺失,其特征是SOX2+的缺失;GATA4 -细胞。我们进一步表明,Fgf20的缺失并不会单独影响胃发育,也不会改变Fgf9LacZ/LacZ表型。结论:Fgf9在胃发育过程中驱动胃的生长和鳞状上皮的特性。
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引用次数: 0
An analysis of contractile and protrusive cell behaviors at the superficial surface of the zebrafish neural plate 斑马鱼神经板表面收缩和突起细胞行为的分析。
IF 1.5 3区 生物学 Q2 ANATOMY & MORPHOLOGY Pub Date : 2025-02-22 DOI: 10.1002/dvdy.70001
Claudio Araya, Raegan Boekemeyer, Francesca Farlie, Lauren Moon, Freshta Darwish, Chris Rookyard, Leanne Allison, Gema Vizcay-Barrena, Roland Fleck, Millaray Aranda, Masa Tada, Jonathan D. W. Clarke

Background

The forces underlying convergence and internalization of the teleost neural plate remain unknown. To help understand this morphogenesis, we analyzed collective and individual cell behaviors at the superficial surface of the neural plate as internalization begins to form the neural keel in the hindbrain region of the zebrafish embryo.

Results

Convergence to the midline is not accompanied by anteroposterior elongation at this stage, and it is characterized by oscillatory contractile behaviors at the superficial surface of the neural plate, a punctate distribution of Cdh2 and medially polarized actin-rich protrusions at the surface of the neural plate. We also characterize the intimate relationship and dynamic protrusive cell behaviors between the surfaces of the motile neural plate and the stationary overlying non-neural enveloping layer.

Conclusions

Superficial neural plate cells are coupled by a punctate distribution of Cdh2-rich adhesions. At this surface, cells tug on neighbors using oscillatory contractions. Oscillatory contractions accompany convergence and shrinkage of the cells' superficial surface for internalization during keeling. Some shrinkage for internalization occurs without oscillations. The deep surface of the overlying non-neural enveloping layer is in contact with the superficial surface of the neural plate, suggesting that it may constrain the neural plate movements of convergence and internalization.

背景:硬骨鱼神经板趋同和内化背后的力量尚不清楚。为了帮助理解这种形态发生,我们分析了内化开始在斑马鱼胚胎后脑区域形成神经龙骨时,神经板表面的集体和个体细胞行为。结果:在此阶段,向中线的收敛不伴有前后伸长,其特征是神经板表面的振荡收缩行为,Cdh2的点状分布和神经板表面内侧极化的富含肌动蛋白的突起。我们还描述了运动神经板表面和静止覆盖的非神经包络层之间的亲密关系和动态突起细胞行为。结论:浅表神经板细胞以点状分布的富cdh2粘连偶联。在这个表面上,细胞通过振荡收缩来拉扯邻近的细胞。振荡收缩伴随着细胞表面的收敛和收缩,以便在龙骨过程中内化。内化的一些收缩发生时没有振荡。上覆非神经包络层的深表面与神经板的浅表面接触,提示其可能约束神经板的收敛和内化运动。
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引用次数: 0
Loss of the epithelial transcription factor grhl3 leads to variably penetrant developmental phenotypes in zebrafish 斑马鱼上皮转录因子grhl3的缺失导致不同的渗透发育表型。
IF 1.5 3区 生物学 Q2 ANATOMY & MORPHOLOGY Pub Date : 2025-02-20 DOI: 10.1002/dvdy.70003
Nishanthi Mathiyalagan, Travis K. Johnson, Zachary Di Pastena, Jarrad N. Fuller, Lee B. Miles, Sebastian Dworkin

Background

Environmental influence is critical for embryogenesis but is significantly under-appreciated under lab conditions, which are not typically designed to robustly test environmental variability. Here, we report environmental effects on the developmental phenotype of zebrafish lacking the transcription factor Grainyhead-like 3 (grhl3), a highly conserved gene that is pivotal in epithelial barrier formation, neurulation, craniofacial development, and convergence-extension.

Results

We had previously reported that deletion of grhl3 led to embryonic lethality by 11 h post-fertilization (hpf); however, housing these grhl3-lines in a different aquatic facility led to substantial differences in phenotypic presentation in grhl3-nullizygous (grhl3−/−) embryos. We found that grhl3−/− embryos presented with three distinct phenotypes, characterized by significant reductions in body length, aberrant orofacial cavity formation and craniofacial morphogenesis and impaired intestinal barrier maintenance.

Conclusions

Our study describes a new model of partial phenotypic penetrance in genetically identical embryos. This may serve as a valuable model system in which to understand gene–environment interactions in developmental and epithelial homeostasis.

背景:环境影响对胚胎发生至关重要,但在实验室条件下被严重低估,而实验室条件通常不能可靠地测试环境变异性。在这里,我们报道了环境对缺乏转录因子Grainyhead-like 3 (grhl3)的斑马鱼发育表型的影响,grhl3是一种高度保守的基因,在上皮屏障形成、神经发育、颅面发育和趋同延伸中起关键作用。结果:我们之前报道过grhl3缺失导致受精后11小时胚胎死亡(hpf);然而,将这些grhl3系置于不同的水生设施中会导致grhl3-/-无合子(grhl3-/-)胚胎的表型表现存在实质性差异。我们发现grhl3-/-胚胎呈现出三种不同的表型,其特征是体长显著减少,口面腔形成和颅面形态发生异常,肠屏障维持受损。结论:我们的研究描述了一个基因相同胚胎的部分表型外显率的新模型。这可能是一个有价值的模型系统,其中理解发育和上皮稳态中的基因-环境相互作用。
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引用次数: 0
β-Catenin localization in the ctenophore Mnemiopsis leidyi suggests an ancestral role in cell adhesion and nuclear function β-连环蛋白在栉水母中的定位提示其在细胞粘附和细胞核功能中的祖先作用。
IF 1.5 3区 生物学 Q2 ANATOMY & MORPHOLOGY Pub Date : 2025-02-20 DOI: 10.1002/dvdy.70004
Brian M. Walters, Lucas J. Guttieres, Mayline Goëb, Stanley J. Marjenberg, Mark Q. Martindale, Athula H. Wikramanayake

Background

The emergence of multicellularity in animals marks a pivotal evolutionary event, which was likely enabled by molecular innovations in the way cells adhere and communicate with one another. β-Catenin is significant to this transition due to its dual role as both a structural component in the cadherin–catenin complex and as a transcriptional coactivator involved in the Wnt/β-catenin signaling pathway. However, our knowledge of how this protein functions in ctenophores, one of the earliest diverging metazoans, is limited.

Results

To study β-catenin function in the ctenophore Mnemiopsis leidyi, we generated affinity-purified polyclonal antibodies targeting Mlβ-catenin. We then used this tool to observe β-catenin protein localization in developing Mnemiopsis embryos. In this article, we provide evidence of consistent β-catenin protein enrichment at cell–cell interfaces in Mnemiopsis embryos. Additionally, we found β-catenin enrichment in some nuclei, particularly restricted to the oral pole around the time of gastrulation. The Mlβ-catenin affinity-purified antibodies now provide us with a powerful reagent to study the ancestral functions of β-catenin in cell adhesion and transcriptional regulation.

Conclusions

The localization pattern of embryonic Mlβ-catenin suggests that this protein had an ancestral role in cell adhesion and may have a nuclear function as well.

背景:动物多细胞的出现标志着一个关键的进化事件,这可能是由细胞粘附和相互沟通方式的分子创新所实现的。β-Catenin对这种转变很重要,因为它既是cadherin-catenin复合物的结构成分,又是Wnt/ β-Catenin信号通路的转录辅激活因子。然而,我们对这种蛋白质如何在栉水母(最早分化的后生动物之一)中发挥作用的了解有限。结果:为了研究β-catenin在栉水母中的功能,我们制备了靶向l - β-catenin的亲和纯化多克隆抗体。然后,我们使用该工具观察发育中的记忆藻胚胎中β-catenin蛋白的定位。在这篇文章中,我们提供了在记忆藻胚胎的细胞-细胞界面上一致的β-catenin蛋白富集的证据。此外,我们发现β-连环蛋白在一些细胞核中富集,特别是在原肠胚形成前后仅限于口极。l - β-catenin亲和纯化抗体为研究β-catenin在细胞粘附和转录调控中的祖先功能提供了强有力的试剂。结论:胚胎ml - β-catenin的定位模式提示该蛋白在细胞粘附中具有祖先作用,并可能具有细胞核功能。
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引用次数: 0
Active cell proliferation contributes to the enlargement of the nascent nucleus pulposus 活跃的细胞增殖有助于新生髓核的增大。
IF 1.5 3区 生物学 Q2 ANATOMY & MORPHOLOGY Pub Date : 2025-02-20 DOI: 10.1002/dvdy.70005
Rose G. Long, Changhee Lee, Clifford J. Tabin

Background

The notochord is an embryonic organ involved in forming and patterning the spinal column. The mechanism by which the notochord transforms from a continuous rod to a segmented structure excluded from the vertebrae and residing solely as the nucleus pulposus within the intervertebral disc is understudied. The current model of notochordal segmentation suggests that swelling through formation and maturation of the vertebrate cartilage squeezes the notochord cells from the vertebra.

Results

Analysis of Collagen 10, a marker for hypertrophic differentiation, as well as evaluation of changes in cell density, reveal that the expansion of the vertebral precursor cells occurs after notochord segmentation has already taken place. We find that the bulk of the nucleus pulposus is derived from accelerated proliferation within the nucleus pulposus itself. In a model of cell proliferation, the increased proliferation at the nucleus pulposus importantly contributes to expand the nucleus pulposus area.

Conclusions

Our data is consistent with the hypothesis that notochord cell proliferation contributes to the enlargement of the nucleus pulposus before the vertebra undergo hypertrophy.

背景:脊索是参与脊柱形成和定型的胚胎器官。脊索从一个连续的杆状结构转变为一个节段结构的机制,排除在椎骨之外,仅作为椎间盘内的髓核存在,其机制尚未得到充分研究。目前的脊索分割模型表明,脊椎动物软骨形成和成熟过程中的肿胀挤压了脊索细胞。结果:对肥大分化标志物胶原10的分析,以及对细胞密度变化的评估显示,椎体前体细胞的扩张发生在脊索分割已经发生之后。我们发现髓核的大部分来自髓核本身的加速增殖。在细胞增殖模型中,髓核处增殖的增加对髓核面积的扩大有重要作用。结论:我们的数据与假设一致,即脊索细胞增殖有助于在椎体肥大之前扩大髓核。
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引用次数: 0
Editorial highlights 社论强调
IF 1.5 3区 生物学 Q2 ANATOMY & MORPHOLOGY Pub Date : 2025-02-10 DOI: 10.1002/dvdy.773
Paul A. Trainor
<p>Every organism is a model organism for understanding development, evolution, disease, and regeneration, and we have only begun to scratch the surface of the interdisciplinary genetic, molecular, cellular, and developmental mechanisms that regulate these biological processes. These “Highlights” denote exciting advances recently reported in <i>Developmental Dynamics</i> that illustrate the complex dynamics of developmental biology.</p><p><b>Embryology</b> “Embryology of the fat-tailed dunnart (<i>Sminthopsis crassicaudata</i>): A marsupial model for comparative mammalian developmental and evolutionary biology” by Axel Newton, Jennifer Hutchison, Ella Farley, Emily Scicluna, Neil Youngson, Jun Liu, Brandon Menzies, Thomas Hildebrandt, Ben Lawrence, Angus Sutherland, David Potter, Gerard Tarulli, Lynne Selwood, Stephen Frankenberg, Sara Ord, and Andrew Pask. <i>Dev Dyn</i>. 254.2, pp. 142–157. https://doi.org/10.1002/dvdy.711. Welcome to the fat-tailed dunnart that is making a name for itself as a marsupial model for developmental, evolutionary, and ecological studies. Marsupials currently remain underutilized in developmental biology studies, which limits our understanding of mammalian diversity. Mammals are a highly diverse lineage of vertebrates, comprising nearly 6500 extant species, classified into three clades: Prototheria, Metatheria, and Eutheria, also known as monotreme, marsupial, and placental mammals, respectively. The fat-tailed dunnart is an emerging laboratory animal, and in this study, the authors stablished methods to confirm pregnancy and generate timed embryos. This facilitated the collection and description of dunnart embryo development from cleavage to birth. Furthermore, detailed descriptions of dunnart organogenesis and heterochronic growth patterns, especially in comparisons with other species, highlight the dunnart's accelerated craniofacial and limb development, which are characteristic of marsupials. This makes the dunnart a valuable model system for investigating the molecular and cellular mechanisms’ underlying heterochrony.</p><p>In an accompanying study, “Breeding fat-tailed dunnarts (<i>Sminthopsis crassicaudata</i>) in captivity: revised practices to minimise stress whilst maintaining considerations of wild biology” by Emily Scicluna, Axel Newton, Jennifer Hutchison, Alicia Dimovski, Kerry Fanson, Gail D'Souza, Shiralee Whitehead and Andrew Pask (need to add in doi number and make sure its linked to web), the authors re-examine current captive management techniques for dunnarts, which rely on scent marking for their social communication and interactions. Although dunnarts have been successfully bred in captivity for decades, there are conflicting reports about best practices for the long-term maintenance of this species. The results of this study provide evidence for preferred cage base substrate types and establish and validate methodology for quantifying stress using fecal glucocorticoid metabolite levels as an i
由Sarah Lusk, Sarah LaPotin, Jason Presnell和Kristen Kwan撰写的“过度活跃的刺猬信号下游增加的Netrin破坏视裂隙的形成”。devdyn . 254.2, pp. 158-173。https://doi.org/10.1002/dvdy.733。眼睛是一个充满液体的球体,周围有三层不同的组织层。眼睛三维结构的缺陷对视力至关重要,可能导致视力障碍。例如,在世界范围内造成儿童失明的一个重要原因是虹膜性结肠瘤,它是由于胚胎发育过程中视神经裂隙发育不全造成的。视神经裂隙是视网膜神经节细胞轴突离开眼睛和脉管系统进入眼睛的通道。人类遗传学研究和动物模型研究表明,结肠瘤的遗传原因是异质性的。相比之下,我们对驱动结肠瘤发病机制的细胞和分子机制的理解仍然知之甚少。在这项研究中,作者将重点放在了刺猬(Hh)信号,这是正常视裂隙发育的核心,更具体地说,是已知的Hh信号的转录靶点,并在适当的时间和地点表达以影响视裂隙和柄的形态发生的细胞间信号分子。Netrin就是这样一个因子,主要以其在轴突引导中的作用而闻名,在这里,作者使用斑马鱼的功能丧失模型来描述Netrin在早期眼睛发育中的新作用。Netrin是足够的,但不是必需的,以破坏过度活跃的Hh信号下游的视裂隙形成。Halie Vitali, Bryce Kuschel, Chhiring Sherpa, Brendan Jones, Nisha Jacob和Syeda Madiha的“缺氧可能通过VEGF-R2和sox17介导的信号传导调节发育中的冠状动脉血管生成”。开发动态,254.2,pp. 174-188。https://doi.org/10.1002/dvdy.750。冠状动脉是为心肌提供氧气和营养的大血管。它们参与心肌梗死的发病机制,可导致心力衰竭,冠状动脉相关疾病是全球死亡的主要原因之一。目前还没有治愈受损冠状动脉的方法,但作者假设,更好地理解胚胎中冠状动脉发育的机制和信号,可以利用并潜在地在成人中重新激活修复和再生受损的冠状动脉。缺氧是众所周知的血管和心肌细胞生长的刺激物,也可能促进冠状动脉血管生成。同样,SOX17对动脉分化和促进血管新生也很重要。在这项研究中,作者利用体内和体外模型模拟细胞对缺氧条件增加或减少的反应,分析缺氧/VEGF-A信号在冠状血管心肌生长中的作用,并确定SOX17是否通过缺氧介导的信号轴在冠状血管形成的调节中起作用。作者得出结论,缺氧确实通过VEGF-R2和SOX17途径调控了冠状动脉的生长发育,从而揭示了冠状血管发育的机制。
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引用次数: 0
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Developmental Dynamics
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