Orchestrating transcriptional control of adult neurogenesis

Abstract

Stem cells have captured our imagination and generated hope, representing a source of replacement cells to treat a host of medical conditions. Tucked away in specialized niches, stem cells maintain tissue function and rejuvenate organs. Balancing the equation between cellular supply and demand is especially important in the adult brain, as neural stem cells (NSCs) in two discrete regions, the subgranular zone (SGZ) of the dentate gyrus and the subventricular zone (SVZ) next to the lateral ventricles, continuously self-renew and differentiate into neurons in a process called adult neurogenesis. Through the interplay of intrinsic and extrinsic factors, adult neurogenic niches ensure neuronal turnover throughout life, contributing to plasticity and homeostatic processes in the brain. This review summarizes recent progress on the molecular control of adult neurogenesis in the SGZ and SVZ, focusing on the role of specific transcription factors that mediate the progression from NSCs to lineage-committed progenitors and, ultimately, the generation of mature neurons and glia.

Figure 1.

Adult neurogenesis in the SGZ of the dentate gyrus within the hippocampus. (A) Sagittal view of the rodent brain with the boxed region outlining hippocampal formation. (B) Schematic of the hippocampus with CA1, CA3, dentate gyrus (DG), and hilus regions. (C) The SGZ niche is comprised of radial and horizontal type 1 NSCs (pink), early stage type 2a TAPs (orange), late stage type 3 TAPs (yellow), immature granule neurons (green), and mature granule neurons (blue). The progression from type 1 NSCs to mature granule neurons in adult SGZ is a multistep process with distinct stages (labeled on top) and is controlled by the sequential expression of transcription factors (bottom colored panels). (ML) Molecular layer; (GCL) granule cell layer.

Figure 2.

Adult neurogenesis in the SVZ and RMS. (A) Sagittal view of the rodent brain, with the boxed region outlining the SVZ region next to the lateral ventricle (LV). (B) Schematic of the SVZ with ependymal cells (E), blood vessel cells (BV), and distinct stem/progenitor cell types (types B, C, and A). (C) The SVZ niche is comprised of astrocyte-like type B1 and B2 NSCs (pink), type C TAPs (orange), type A neuroblasts (yellow), immature neurons (green), and mature neurons (blue). The progression from type B NSCs to mature neurons in the adult SVZ is a multistep process with distinct stages (labeled on top) and is controlled by the sequential expression of transcription factors (bottom colored panels).