University of North Carolina, Chapel Hill, NC 27599, USA.
Neuron. 2011 Jan 13;69(1):91-105. doi: 10.1016/j.neuron.2010.12.003.
We have established functions of the stimulus-dependent MAPKs, ERK1/2 and ERK5, in DRG, motor neuron, and Schwann cell development. Surprisingly, many aspects of early DRG and motor neuron development were found to be ERK1/2 independent, and Erk5 deletion had no obvious effect on embryonic PNS. In contrast, Erk1/2 deletion in developing neural crest resulted in peripheral nerves that were devoid of Schwann cell progenitors, and deletion of Erk1/2 in Schwann cell precursors caused disrupted differentiation and marked hypomyelination of axons. The Schwann cell phenotypes are similar to those reported in neuregulin-1 and ErbB mutant mice, and neuregulin effects could not be elicited in glial precursors lacking Erk1/2. ERK/MAPK regulation of myelination was specific to Schwann cells, as deletion in oligodendrocyte precursors did not impair myelin formation, but reduced precursor proliferation. Our data suggest a tight linkage between developmental functions of ERK/MAPK signaling and biological actions of specific RTK-activating factors.
我们已经确定了刺激依赖性 MAPKs（ERK1/2 和 ERK5）在背根神经节、运动神经元和雪旺细胞发育中的功能。令人惊讶的是，我们发现早期背根神经节和运动神经元发育的许多方面都与 ERK1/2 无关，而 Erk5 的缺失对胚胎周围神经系统没有明显影响。相比之下，发育中的神经嵴中 Erk1/2 的缺失导致周围神经中缺乏雪旺细胞前体，而 Erk1/2 在雪旺细胞前体中的缺失导致分化中断和轴突明显少突胶质化。雪旺细胞表型与神经调节蛋白-1 和 ErbB 突变小鼠中报道的表型相似，并且在缺乏 Erk1/2 的神经胶质前体中不能引发神经调节蛋白的作用。ERK/MAPK 对髓鞘形成的调节特异性地针对雪旺细胞，因为少突胶质前体中的缺失不会损害髓鞘形成，但会减少前体细胞的增殖。我们的数据表明，ERK/MAPK 信号传导的发育功能与特定 RTK 激活因子的生物学作用之间存在紧密联系。
