Cooperation between sonic hedgehog and fibroblast growth factor/MAPK signalling pathways in neocortical precursors
Cooperation between sonic hedgehog and fibroblast growth factor/MAPK signalling pathways in neocortical precursors
复制标题
DOI：
10.1242/dev.01027
复制
发表时间：
2004-03-01
期刊：
影响因子：
4.6
通讯作者：
Richardson, WD
中科院分区：
文献类型：
--
作者：
Kessaris, N;Jamen, F;Richardson, WD
Sonic hedgehog（SHH）和成纤维细胞生长因子2（FGF2）都可以诱导新皮质前体表达转录因子OLIG2，并在培养中产生少突胶质细胞祖细胞（OLP）。FGF 2的活性不受环巴胺的影响，环巴胺阻断Hedgehog信号传导，表明OLP产生的FGF途径是Hedgehog独立的。出乎意料的是，SHH介导的OLP诱导被PD173074阻断，PD173074是FGF受体（FGFR）酪氨酸激酶的选择性抑制剂。SHH活性也依赖于丝裂原活化蛋白激酶（MAPK），但SHH本身不激活MAPK。相反，FGFR的组成性活性维持了SHH的OLIG2和OLP诱导活性绝对需要的磷酸化MAPK的基础水平。用编码组成型活性RAS的逆转录病毒刺激MAPK途径表明，对MAPK的需求是细胞自主的，即在成为OLP的细胞中需要MAPK与SHH信号传导一起。
Sonic hedgehog (SHH) and fibroblast growth factor 2 (FGF2) can both induce neocortical precursors to express the transcription factor OLIG2 and generate oligodendrocyte progenitors (OLPs) in culture. The activity of FGF2 is unaffected by cyclopamine, which blocks Hedgehog signalling, demonstrating that the FGF pathway to OLP production is Hedgehog independent. Unexpectedly, SHH-mediated OLP induction is blocked by PD173074, a selective inhibitor of FGF receptor (FGFR) tyrosine kinase. SHH activity also depends on mitogen-activated protein kinase (MAPK) but SHH does not itself activate MAPK. Instead, constitutive activity of FGFR maintains a basal level of phosphorylated MAPK that is absolutely required for the OLIG2- and OLP-inducing activities of SHH. Stimulating the MAPK pathway with a retrovirus encoding constitutively active RAS shows that the requirement for MAPK is cell-autonomous, i.e. MAPK is needed together with SHH signalling in the cells that become OLPs.