Abstract
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.
Highlights
Embryonic brain development is a complex process that includes the proliferation and differentiation of neural stem cells (NSCs) and neural progenitor cells (NPCs), neuronal migration and polarity establishment [1,2,3,4]
At the peak stage of neocortical neurogenesis (E13.5), immunostaining showed that Kinesin family member 2a (Kif2a) was expressed throughout the whole neocortex (Fig 1B, left)
Quantitative analysis showed that the percentage of cells expressing Kif2a over the whole neocortex was gradually reduced in the VZ/SVZ from E13.5 to E17.5 but was significantly increased in the intermediate zone (IZ) at E15.5 and in the cortical plate (CP) at E17.5 (Fig 1C), indicating that Kif2a may play multiple roles with spatially and temporally distinct localization
Summary
Embryonic brain development is a complex process that includes the proliferation and differentiation of neural stem cells (NSCs) and neural progenitor cells (NPCs), neuronal migration and polarity establishment [1,2,3,4]. In the ventricular zone/subventricular zone (VZ/SVZ), NSCs/NPCs originated from neuroepithelial cells continuously proliferate and produce new neurons to form a six-layered laminar structure, which is necessary for proper brain functions [5,6]. During the peak stage of embryonic neurogenesis, NSCs/NPCs from embryonic day 13.5 (E13.5) mainly undergo asymmetric divisions to self-renewal and generate one neuron or one intermediate progenitor cell (IPC), which subsequently divides symmetrically in the SVZ and differentiates into two neurons [7]. Regulation of NPC proliferation and differentiation by Kif2a Several signaling pathways are known to be involved in neocortical neurogenesis: for example, the canonical Wnt signaling pathway
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