Sleep or deplete: how the choroid plexus helps to keep neural stem cells in balance

Abstract

The activity of stem cells in the adult brain is controlled by various niche-dependent mechanisms. A new article by Lepko et al (2019) shows that proliferation of neural stem cells in the ventricular-subventricular zone is regulated by choroid plexus-derived miR-204, identifying a novel mechanism of how the delicate balance between stem cell quiescence and activation is controlled.

Figure 1. Choroid plexus‐derived miR‐204 regulates neural stem cell quiescence in the adult brain

Adult neurogenesis occurs in two distinct regions in the brain, the ventricular–subventricular zone (V‐SVZ) and the dentate gyrus of the hippocampus. In the V‐SVZ, neural stem cells (NSCs, type B cells) can divide and give rise to transit‐amplifying cells (type C cells) that proliferate and generate neuroblasts (type A cells). Neuroblasts migrate along the rostral migratory stream (RMS) to the olfactory bulb (OB), where they differentiate into interneurons and contribute to the neuronal network. The activity of type B cells is controlled by signals derived from adjacent cells (e.g. ChAT⁺ neurons), neighbouring vasculature, the cerebrospinal fluid (CSF) and also long‐distance cells (e.g. POMC⁺ hypothalamic neurons). Lepko et al (2019) discovered a novel miR‐204‐based mechanism that regulates the maintenance and activation of quiescent, label‐retaining NSCs and shows that miR‐204 controls neuronal priming of NSCs in the V‐SVZ. The choroid plexus (ChP) secretes vesicles containing miR‐204 into the cerebrospinal fluid that are taken up by NSCs. miR‐204 prevents the translation of neuronal fate determinants, such as Meis2, and prevents the premature activation of quiescent NSCs.