TGFβ1a regulates zebrafish posterior lateral line formation via Smad5 mediated pathway
TGFβ1a regulates zebrafish posterior lateral line formation via Smad5 mediated pathway
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TGFβ1a 通过 Smad5 介导的途径调节斑马鱼后侧线形成
DOI：
10.1093/jmcb/mjv004
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发表时间：
2015-02-01
影响因子：
5.5
通讯作者：
Jia, Shunji
中科院分区：
文献类型：
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作者：
Xing, Cencan;Gong, Bo;Jia, Shunji
斑马鱼感觉后侧线（pLL）已成为研究集体细胞迁移和细胞形态发生的一个有吸引力的模型。最近的研究表明，趋化因子，Wnt/β-catenin，Fgf和Delta-Notch信号通路参与调节pLL的发展。然而，目前尚不清楚TGF β信号通路是否参与pLL的发展。在这里，我们报告了TGF β 1在调节pLL原基（pLLP）的形态发生中的关键作用。tgf β 1a基因在侧线原基中大量表达。tgf β 1a的敲除导致神经肥大数量减少，神经肥大间距离增加，毛细胞数量减少。TGF β 1a缺失的胚胎中的异常形态发生与atoh 1a、deltaA和n-cadherin/cdh 2的表达减少相关，这些是已知的pLLP形态发生的重要调节因子。与tgf β 1a耗竭类似，pLLP中表达的Smad 5的敲除影响pLLP发育，而组成型活性Smad 5同种型的过表达挽救了tgf β 1a耗竭胚胎中的缺陷，表明Smad 5介导tgf β 1a在pLLP发育中的功能。因此，TGF β/Smad 5信号在斑马鱼侧线形成中起着重要作用。
The zebrafish sensory posterior lateral line (pLL) has become an attractive model for studying collective cell migration and cell morphogenesis. Recent studies have indicated that chemokine, Wnt/beta-catenin, Fgf, and Delta-Notch signaling pathways participate in regulating pLL development. However, it remains unclear whether TGF beta signaling pathway is involved in pLL development. Here we report a critical role of TGF beta 1 in regulating morphogenesis of the pLL primordium (pLLP). The tgf beta 1a gene is abundantly expressed in the lateral line primordium. Knockdown or knockout of tgf beta 1a leads to a reduction of neuromast number, an increase of inter-neuromast distance, and a reduced number of hair cells. The aberrant morphogenesis in embryos depleted of tgf beta 1a correlates with the reduced expression of atoh1a, deltaA, and n-cadherin/cdh2, which are known important regulators of the pLLP morphogenesis. Like tgf beta 1a depletion, knockdown of smad5 that expresses in the pLLP, affects pLLP development whereas overexpression of a constitutive active Smad5 isoform rescues the defects in embryos depleted of tgf beta 1a, indicating that Smad5 mediates tgf beta 1a function in pLLP development. Therefore, TGF beta/Smad5 signaling plays an important role in the zebrafish lateral line formation.