The timing of emergence of muscle progenitors is controlled by an FGF/ERK/SNAIL1 pathway
The timing of emergence of muscle progenitors is controlled by an FGF/ERK/SNAIL1 pathway
复制标题
DOI：
10.1016/j.ydbio.2009.05.544
复制
发表时间：
2009-09-15
影响因子：
2.7
通讯作者：
Marcelle, Christophe
中科院分区：
文献类型：
--
作者：
Delfini, Marie-Claire;De La Celle, Marie;Marcelle, Christophe
皮肌节是躯干和四肢所有骨骼肌的来源。躯干骨骼肌的形成分为两个连续的阶段：在第一阶段，位于上皮真皮肌节的四个边界处的细胞分层以产生由有丝分裂后的单核肌细胞组成的初级肌节。中央皮肌节的上皮-间质转化（EMT）启动肌肉形成的第二阶段，其特征在于有丝分裂的肌肉祖细胞从皮肌节的中央区域大量进入初级肌节。调节皮肌节EMT时间的信号是未知的。在这里，我们建议，这一进程是由FGF信号从主要的肌节，一个已知的来源FGF。FGF的过表达导致皮肌节的早熟EMT，而相反，通过显性负性形式的FGFR 4的电穿孔抑制FGF信号传导延迟了该过程。在真皮肌节内，FGF信号传导触发MAPK/ERK通路，其导致转录因子Snail 1的激活，Snail 1是许多细胞环境中的EMT的已知调节因子。MAPK/ERK通路和Snail 1的激活或抑制模拟FGF信号传导，并分别导致皮肤肌节的早期或延迟EMT。总而言之，我们的研究结果表明，在Aromotes，初级肌节是一个组织中心，调节胚胎肌肉祖细胞的肌肉质量内的及时进入，从而启动躯干骨骼肌的生长阶段。(C)2009 Elsevier Inc. All rights reserved.
In amniotes, the dermomyotome is the source of all skeletal muscles of the trunk and the limbs. Trunk skeletal muscles form in two sequential stages: in the first stage, cells located at the four borders of the epithelial dermomyotome delaminate to generate the primary myotome, composed of post-mitotic, mononucleated myocytes. The epithelio-mesenchymal transition (EMT) of the central dermomyotome initiates the second stage of muscle formation, characterised by a massive entry of mitotic muscle progenitors from the central region of the dermomyotome into the primary myotome. The signals that regulate the timing of the dermomyotome EMT are unknown. Here, we propose that this process is regulated by an FGF signal emanating from the primary myotome, a known source of FGF. The over-expression of FGF results in a precocious EMT of the dermomyotome, while on the contrary, the inhibition of FGF signalling by the electoporation of a dominant-negative form of FGFR4 delays this process. Within the dermomyotome, FGF signalling triggers a MAPK/ERK pathway that leads to the activation of the transcription factor Snail1, a known regulator of EMT in a number of cellular contexts. The activation or the inhibition of the MAPK/ERK pathway and of Snail1 mimics that of FGF signalling and leads to an early or delayed EMT of the dermomyotome, respectively. Altogether, our results indicate that in amniotes, the primary myotome is an organizing center that regulates the timely entry of embryonic muscle progenitors within the muscle masses, thus initiating the growth phase of the trunk skeletal muscles. (C) 2009 Elsevier Inc. All rights reserved.