Pannexin 1 regulates postnatal neural stem and progenitor cell proliferation

We detected pannexin 1 in neural stem and progenitor cells in vitro and in vivo. We manipulated pannexin 1 expression and activity in Neuro2a neuroblastoma cells and primary postnatal neurosphere cultures to demonstrate that pannexin 1 regulates neural stem and progenitor cell proliferation likely through the release of adenosine triphosphate (ATP).Permeable to ATP, a potent autocrine/paracine signaling metabolite, pannexin 1 channels are ideally suited to influence the behavior of neural stem and progenitor cells. Here we demonstrate they play a robust role in the regulation of neural stem and progenitor cell proliferation. Endogenous postnatal neural stem and progenitor cells are crucial for normal brain health, and their numbers decline with age. Furthermore, these special cells are highly responsive to neurological injury and disease, and are gaining attention as putative targets for brain repair. Therefore, understanding the fundamental role of pannexin 1 channels in neural stem and progenitor cells is of critical importance for brain health and disease.The majority of neurons are born embryonically, however neurogenesis continues in the postnatal brain throughout life (reviewed in [1]). Postnatal neurogenesis is a complex, multi-step developmental process that includes cell behaviors such as proliferation, differentiation and migration, and involves several distinct cell types. These stem cell behaviors are guided, in part, by extracellular stimuli unique to their specialized microenvironments or ‘niches’: the subgranular zone (SGZ) of the dentate gyrus and the ventricular zone (VZ) of the lateral ventricles (Figure 1A).Postnatal NSCs in the VZ generate large numbers of olfactory bulb interneurons. The distinct neural stem and progenitor cell (NSC/NPC) types implicated in this neurogenic process are characterized by their morphology and differential expression of lineage markers (Figure 1A). Radial glia-like cells (known as type B cells in VZ) express the fila