Pax3对成纤维细胞生长因子(FGF)信号的调控影响胚胎祖细胞向生肌程序的进展。

Pax3 regulation of FGF signaling affects the progression of embryonic progenitor cells into the myogenic program.

作者信息

Lagha Mounia, Kormish Jay D, Rocancourt Didier, Manceau Marie, Epstein Jonathan A, Zaret Kenneth S, Relaix Frédéric, Buckingham Margaret E

机构信息

CNRS URA 2578, Department of Developmental Biology, Pasteur Institute, 75015 Paris, France.

出版信息

Genes Dev. 2008 Jul 1;22(13):1828-37. doi: 10.1101/gad.477908.

Abstract

Pax3/7-dependent stem cells play an essential role in skeletal muscle development. We now show that Fgfr4 lies genetically downstream from Pax3 and is a direct target. In chromatin immunoprecipitation (ChIP)-on-chip experiments, Pax3 binds to a sequence 3' of the Fgfr4 gene that directs Pax3-dependent expression at sites of myogenesis in transgenic mouse embryos. The activity of this regulatory element is also partially dependent on E-boxes, targets of the myogenic regulatory factors, which are expressed as progenitor cells enter the myogenic program. Other FGF signaling components, notably Sprouty1, are also regulated by Pax3. In vivo manipulation of Sprouty expression reveals that FGF signaling affects the balance between Pax-positive progenitor cells and committed myoblasts. These results provide new insight into the Pax-initiated regulatory network that modulates stem cell maintenance versus tissue differentiation.

摘要

依赖于Pax3/7的干细胞在骨骼肌发育中起着至关重要的作用。我们现在发现Fgfr4在基因上位于Pax3的下游,并且是一个直接靶点。在染色质免疫沉淀芯片实验中,Pax3与Fgfr4基因3'端的一个序列结合,该序列在转基因小鼠胚胎的肌发生位点指导依赖于Pax3的表达。这个调控元件的活性也部分依赖于E盒,即生肌调节因子的靶点,当祖细胞进入生肌程序时它们会表达。其他FGF信号成分,尤其是Sprouty1,也受Pax3调控。对Sprouty表达的体内操作表明,FGF信号影响Pax阳性祖细胞和已定向的成肌细胞之间的平衡。这些结果为调节干细胞维持与组织分化的Pax启动的调控网络提供了新的见解。

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