SRF regulates craniofacial development through selective recruitment of MRTF cofactors by PDGF signaling.
SRF regulates craniofacial development through selective recruitment of MRTF cofactors by PDGF signaling.
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DOI：
10.1016/j.devcel.2014.10.005
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发表时间：
2014-11-10
影响因子：
11.8
通讯作者：
Soriano, Philippe
中科院分区：
文献类型：
--
作者：
Vasudevan, Harish N.;Soriano, Philippe
受体酪氨酸激酶信号传导对哺乳动物颅面发育至关重要，但关键的下游转录效应子仍然未知。我们证明，SRF是由小鼠胚胎腭间充质细胞的PDGF和FGF信号转导诱导的，并且SRF神经嵴条件突变体表现出伴随增殖和迁移缺陷的面部裂开。Srf和Pdgfra突变体在颅面发育中相互作用，但Srf和Fgfr 1突变体不相互作用。这种信号特异性在辅因子激活水平上得到了重现：虽然PDGF和FGF靶基因启动子都显示出与SRF ChIP-seq峰的富集的全基因组重叠，但PDGF选择性地激活MRTF依赖性细胞骨架基因的网络。总的来说，我们的研究结果确定了一个新的作用，SRF在颅面发育过程中的增殖和迁移，并描绘了受体酪氨酸激酶特异性介导的机制，通过差异辅因子的使用，导致一个独特的PDGF响应SRF驱动的转录程序中面。
Receptor tyrosine kinase signaling is critical for mammalian craniofacial development, but the key downstream transcriptional effectors remain unknown. We demonstrate that SRF is induced by both PDGF and FGF signaling in mouse embryonic palatal mesenchyme cells, and Srf neural crest conditional mutants exhibit facial clefting accompanied by proliferation and migration defects. Srf and Pdgfra mutants interact genetically in craniofacial development, but Srf and Fgfr1 mutants do not. This signal specificity is recapitulated at the level of cofactor activation: while both PDGF and FGF target gene promoters show enriched genome-wide overlap with SRF ChIP-seq peaks, PDGF selectively activates a network of MRTF-dependent cytoskeletal genes. Collectively, our results identify a novel role for SRF in proliferation and migration during craniofacial development and delineate a mechanism of receptor tyrosine kinase specificity mediated through differential cofactor usage, leading to a unique PDGF-responsive SRF-driven transcriptional program in the midface.
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