AQP4 knockout impairs proliferation, migration and neuronal differentiation of adult neural stem cells

Aquaporin-4 (AQP4), a key molecule for maintaining water and ion homeostasis in the central nervous system, is expressed in adult neural stem cells (ANSCs) as well as astrocytes. However, little is known about the functions of AQP4 in the ANSCs in vitro. Here we show that AQP4 knockout inhibits the proliferation, survival, migration and neuronal differentiation of ANSCs derived from the subventricular zone of adult mice. Flow cytometric cell cycle analysis revealed that AQP4 knockout increased the basal apoptosis and induced a G2-M arrest in ANSCs. Using Fluo-3 Ca²⁺ imaging, we show that AQP4 knockout alters the spontaneous Ca²⁺ oscillations by frequency enhancement and amplitude suppression, and suppresses KCl-induced Ca²⁺ influx. AQP4 knockout downregulated the expression of connexin43 and the L-type voltage-gated Ca²⁺ channel CaV1.2 subtype in ANSCs. Together, these findings suggest that AQP4 plays a crucial role in regulating the proliferation, migration and differentiation of ANSCs, and this function of AQP4 is probably mediated by its action on intracellular Ca²⁺ dynamics.