FGF acts directly on the somitic tendon progenitors through the Ets transcription factors Pea3 and Erm to regulate scleraxis expression
FGF acts directly on the somitic tendon progenitors through the Ets transcription factors Pea3 and Erm to regulate scleraxis expression
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DOI：
10.1242/dev.01275
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发表时间：
2004-08-01
期刊：
影响因子：
4.6
通讯作者：
Tabin, CJ
中科院分区：
文献类型：
--
作者：
Brent, AE;Tabin, CJ
在肌小体发育过程中，肌节分泌的成纤维细胞生长因子信号诱导在肌节中的肌腱祖细胞群中形成表达硬化轴(SCX)的肌腱祖细胞群，在肌肉和软骨的未来谱系之间的交界处。虽然过表达研究表明整个菌核能够表达SCX以响应成纤维细胞生长因子信号，但正常的SCX表达结构域仅包括前后背部菌核。为了了解这种限制的分子基础，我们研究了一组涉及成纤维细胞生长因子信号转导的基因的表达，发现Fgf8共表达组中的几个成员与SCX在背部核心体中共表达。特别令人感兴趣的是ETS转录因子Pea3和Erm，它们作为成纤维细胞生长因子信号的转录效应因子发挥作用。我们的研究表明Pea3和Erm的转录激活对于SCX在体节中的表达是必要和充分的，并提出了躯体肌腱祖细胞的结构域既受Pea3和Erm的限制表达，又受这些ETS转录因子和起源于肌节的成纤维细胞生长因子信号之间的精确空间关系的调控。
During somite development, a fibroblast growth factor (FGF) signal secreted from the myotome induces formation of a scleraxis (Scx)-expressing tendon progenitor population in the sclerotome, at the juncture between the future lineages of muscle and cartilage. While overexpression studies show that the entire sclerotome is competent to express Scx in response to FGF signaling, the normal Scx expression domain includes only the anterior and posterior dorsal sclerotome. To understand the molecular basis for this restriction, we examined the expression of a set of genes involved in FGF signaling and found that several members of the Fgf8 synexpression group are co-expressed with Scx in the dorsal sclerotome. Of particular interest were the Ets transcription factors Pea3 and Erm, which function as transcriptional effectors of FGF signaling. We show here that transcriptional activation by Pea3 and Erm in response to FGF signaling is both necessary and sufficient for Scx expression in the somite, and propose that the domain of the somitic tendon progenitors is regulated both by the restricted expression of Pea3 and Erm, and by the precise spatial relationship between these Ets transcription factors and the FGF signal originating in the myotome.