Shroom3 is required downstream of FGF signalling to mediate proneuromast assembly in zebrafish
Shroom3 is required downstream of FGF signalling to mediate proneuromast assembly in zebrafish
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DOI：
10.1242/dev.083253
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发表时间：
2012-12-15
期刊：
影响因子：
4.6
通讯作者：
Lecaudey, Virginie
中科院分区：
文献类型：
--
作者：
Ernst, Sandra;Liu, Kun;Lecaudey, Virginie
在发育过程中，形态发生过程需要精确协调细胞分化、细胞形状变化以及通常情况下的细胞迁移。然而，模式信息如何被用来协调这些不同的过程仍然不清楚。在侧线形态发生过程中，一组细胞同时迁移和组装径向排列的细胞团，称为花环，预示着侧线感觉器官的形成。这一过程是由成纤维细胞生长因子信号通路控制的，它诱导细胞命运改变、细胞迁移和细胞形状改变。然而，由成纤维细胞生长因子激活诱导的在细胞水平上介导这些变化的确切分子机制尚不清楚。在这里，我们集中在FGFs控制根尖收缩和玫瑰花环组装的机制。我们发现，LL原基的根尖收缩需要非肌肉肌球蛋白的活动。我们进一步证明，shroom3，一种众所周知的非肌肉肌球蛋白活性的调节因子，在LL原基中表达，它的表达需要成纤维细胞生长因子信号。通过功能获得和功能丧失实验，我们证明了Shroom3是玫瑰花环组装过程中细胞形状变化的主要组织者，可能是通过协调Rho激酶募集和非肌肉肌球蛋白激活来实现的。为了以一种公正的方式量化LL原基中的形态发生，我们开发了一种独特的可训练的“玫瑰花环检测器”。因此，我们提出了一个模型，在该模型中，Shroom3以Rho激酶和非肌肉肌球蛋白依赖的方式驱动成纤维细胞生长因子下游L1的玫瑰花结组装。总而言之，我们揭示了在LL感觉器官形成过程中图案化和形态发生之间的第一个机制联系。
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.