The cyclin-dependent kinase inhibitors p57 and p27 regulate neuronal migration in the developing mouse neocortex
The cyclin-dependent kinase inhibitors p57 and p27 regulate neuronal migration in the developing mouse neocortex
复制标题
DOI：
10.1074/jbc.m609944200
复制
发表时间：
2007-01-05
影响因子：
4.8
通讯作者：
Gotoh, Yukiko
中科院分区：
文献类型：
--
作者：
Itoh, Yasuhiro;Masuyama, Norihisa;Gotoh, Yukiko
神经元前体保留在发育中的哺乳动物新皮层的增殖区中，直到它们经历神经元分化和细胞周期停滞之后。新生的神经元然后从增殖区迁移并进入皮质板。协调迁移与神经元分化的分子尚不清楚。我们在这项研究中提出，cdk抑制剂p57和p27在这种协调中发挥作用。我们已经发现，p57和p27 mRNA增加后，神经元分化的新皮层神经上皮细胞。通过RNA干扰敲低p57导致进入皮质板的神经元迁移显著延迟，但不影响神经元分化。敲除p27还抑制中间区以及皮质板中的神经元迁移，如其他人所报道的。我们还发现p27的敲低增加了p57 mRNA水平。这些结果表明，p57和p27在神经元迁移中发挥重要作用，并可能在音乐会上，协调神经元分化，迁移，并可能在新皮层发育的细胞周期阻滞的时间。
Neuronal precursors remain in the proliferative zone of the developing mammalian neocortex until after they have undergone neuronal differentiation and cell cycle arrest. The newborn neurons then migrate away from the proliferative zone and enter the cortical plate. The molecules that coordinate migration with neuronal differentiation have been unclear. We have proposed in this study that the cdk inhibitors p57 and p27 play a role in this coordination. We have found that p57 and p27 mRNA increase upon neuronal differentiation of neocortical neuroepithelial cells. Knockdown of p57 by RNA interference resulted in a significant delay in the migration of neurons that entered the cortical plate but did not affect neuronal differentiation. Knockdown of p27 also inhibits neuronal migration in the intermediate zone as well as in the cortical plate, as reported by others. We have also found that knockdown of p27 increases p57 mRNA levels. These results suggest that both p57 and p27 play essential roles in neuronal migration and may, in concert, coordinate the timing of neuronal differentiation, migration, and possibly cell cycle arrest in neocortical development.