Sun Dong, Zhou Xue, Yu Hua-Li, He Xiao-Xiao, Guo Wei-Xiang, Xiong Wen-Cheng, Zhu Xiao-Juan
Key Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Cytology and Genetics, Northeast Normal University, Changchun, Jilin, China.
Department of Neuroscience & Regenerative Medicine and Department of Neurology, Augusta University, Augusta, Georgia, United States of America.
PLoS One. 2017 Jun 7;12(6):e0179047. doi: 10.1371/journal.pone.0179047. eCollection 2017.
In the developing neocortex, cells in the ventricular/subventricular zone are largely multipotent neural stem cells and neural progenitor cells. These cells undergo self-renewal at the early stage of embryonic development to amplify the progenitor pool and subsequently differentiate into neurons. It is thus of considerable interest to investigate mechanisms controlling the switch from neural stem cells or neural progenitor cells to neurons. Here, we present evidence that Kif2a, a member of the Kinesin-13 family, plays a role in regulating the proliferation and differentiation of neural stem cells or neural progenitor cells at embryonic day 13.5. Silencing Kif2a by use of in utero electroporation of Kif2a shRNA reduced neural stem cells proliferation or self-renewal but increased neuronal differentiation. We further found that knockdown of Kif2a decreased the protein level of β-catenin, which is a critical molecule for neocortical neurogenesis. Together, these results reveal an important function of Kif2a in embryonic neocortical neurogenesis.
在发育中的新皮层中,脑室下区的细胞大多是多能神经干细胞和神经祖细胞。这些细胞在胚胎发育早期进行自我更新,以扩大祖细胞池,随后分化为神经元。因此,研究控制从神经干细胞或神经祖细胞向神经元转变的机制具有相当大的意义。在此,我们提供证据表明,驱动蛋白-13家族成员Kif2a在胚胎第13.5天调节神经干细胞或神经祖细胞的增殖和分化中发挥作用。通过子宫内电穿孔Kif2a短发夹RNA沉默Kif2a可减少神经干细胞增殖或自我更新,但增加神经元分化。我们进一步发现,敲低Kif2a会降低β-连环蛋白的蛋白质水平,而β-连环蛋白是新皮层神经发生的关键分子。这些结果共同揭示了Kif2a在胚胎新皮层神经发生中的重要作用。