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Shroom3 在 FGF 信号下游起作用,以介导斑马鱼的原神经嵴组装。

Shroom3 is required downstream of FGF signalling to mediate proneuromast assembly in zebrafish.

机构信息

Centre for Biological Signalling Studies, University of Freiburg, Schänzlestrasse 18, D-79104 Freiburg, Germany.

出版信息

Development. 2012 Dec;139(24):4571-81. doi: 10.1242/dev.083253. Epub 2012 Nov 7.

DOI:10.1242/dev.083253
PMID:23136387
Abstract

During development, morphogenetic processes require a precise coordination of cell differentiation, cell shape changes and, often, cell migration. Yet, how pattern information is used to orchestrate these different processes is still unclear. During lateral line (LL) morphogenesis, a group of cells simultaneously migrate and assemble radially organized cell clusters, termed rosettes, that prefigure LL sensory organs. This process is controlled by Fibroblast growth factor (FGF) signalling, which induces cell fate changes, cell migration and cell shape changes. However, the exact molecular mechanisms induced by FGF activation that mediate these changes on a cellular level are not known. Here, we focus on the mechanisms by which FGFs control apical constriction and rosette assembly. We show that apical constriction in the LL primordium requires the activity of non-muscle myosin. We demonstrate further that shroom3, a well-known regulator of non-muscle myosin activity, is expressed in the LL primordium and that its expression requires FGF signalling. Using gain- and loss-of-function experiments, we demonstrate that Shroom3 is the main organizer of cell shape changes during rosette assembly, probably by coordinating Rho kinase recruitment and non-muscle myosin activation. In order to quantify morphogenesis in the LL primordium in an unbiased manner, we developed a unique trainable 'rosette detector'. We thus propose a model in which Shroom3 drives rosette assembly in the LL downstream of FGF in a Rho kinase- and non-muscle myosin-dependent manner. In conclusion, we uncovered the first mechanistic link between patterning and morphogenesis during LL sensory organ formation.

摘要

在发育过程中,形态发生过程需要精确协调细胞分化、细胞形状变化,并且常常需要细胞迁移。然而,模式信息如何用于协调这些不同的过程仍然不清楚。在侧线 (LL) 形态发生过程中,一组细胞同时迁移并组装成径向组织的细胞簇,称为玫瑰花结,这些玫瑰花结预形成 LL 感觉器官。这个过程受成纤维细胞生长因子 (FGF) 信号的控制,该信号诱导细胞命运变化、细胞迁移和细胞形状变化。然而,FGF 激活诱导这些细胞水平变化的确切分子机制尚不清楚。在这里,我们专注于 FGF 控制顶壁收缩和玫瑰花结组装的机制。我们表明,LL 原基中的顶壁收缩需要非肌肉肌球蛋白的活性。我们进一步证明,shroom3 是一种众所周知的非肌肉肌球蛋白活性调节剂,在 LL 原基中表达,其表达需要 FGF 信号。通过增益和损失功能实验,我们证明 Shroom3 是玫瑰花结组装过程中细胞形状变化的主要组织者,可能通过协调 Rho 激酶募集和非肌肉肌球蛋白激活。为了以无偏倚的方式定量 LL 原基中的形态发生,我们开发了一种独特的可训练的“玫瑰花结检测器”。因此,我们提出了一个模型,其中 Shroom3 在 FGF 下游以 Rho 激酶和非肌肉肌球蛋白依赖性的方式驱动 LL 中的玫瑰花结组装。总之,我们揭示了在 LL 感觉器官形成过程中模式形成和形态发生之间的第一个机制联系。

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