Abstract
Neural stem cells (NSCs) are primary progenitor cells in the early developmental stage in the brain that initiate a diverse lineage of differentiated neurons and glia. Radial glial cells (RGCs), a type of neural stem cell in the ventricular zone, are essential for nurturing and delivering new immature neurons to the appropriate cortical target layers. Here we report that Anoctamin 1 (ANO1)/TMEM16A, a Ca2+-activated chloride channel, mediates the Ca2+-dependent process extension of RGCs. ANO1 is highly expressed and functionally active in RGCs of the mouse embryonic ventricular zone. Knockdown of ANO1 suppresses RGC process extension and protrusions, whereas ANO1 overexpression stimulates process extension. Among various trophic factors, brain-derived neurotrophic factor (BDNF) activates ANO1, which is required for BDNF-induced process extension in RGCs. More importantly, Ano1-deficient mice exhibited disrupted cortical layers and reduced cortical thickness. We thus conclude that the regulation of RGC process extension by ANO1 contributes to the normal formation of mouse embryonic brain.
Highlights
Neural stem cells (NSCs) are primary progenitor cells in the early developmental stage in the brain that initiate a diverse lineage of differentiated neurons and glia
Anoctamin 1 (ANO1) was highly expressed in the ventricular zone (VZ) and subventricular zone (SVZ) at E12.5 and E14.5, but expression was dramatically decreased at P1 (Fig. 1A)
Tuj-1 immunofluorescence was low at E12.5 but gradually increased from E14.5 to P1 (Fig. 1B). These results suggest that ANO1 is expressed in Radial glial cells (RGCs) in the VZ and SVZ regions but not in neurons of the neonatal brain
Summary
Neural stem cells (NSCs) are primary progenitor cells in the early developmental stage in the brain that initiate a diverse lineage of differentiated neurons and glia. Radial glial cells (RGCs), a type of neural stem cell in the ventricular zone, are essential for nurturing and delivering new immature neurons to the appropriate cortical target layers. Other types of RGCs, such as highly proliferative outer RGCs with a monopolar shape, produce large numbers of neural progenitor cells in the outer SVZ [2, 5]. These outer RGCs act as a scaffold for the cortical architecture and contribute to gyrification of the cortex in primates. The depolarization by Cl− efflux is essential for NSC physiology, the role of chloride channels other than GABAA receptors in NSCs during cortical development remains elusive
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