Signaling in adult neurogenesis

Abstract

Neural stem cells (NSCs) in the adult brain continuously supply new neurons to the hippocampal dentate gyrus (DG) and the olfactory bulb (OB). Recent studies indicate that the progression from neural precursor cells (NPCs) to mature neurons is tightly controlled by coordinate cell-intrinsic programs and external signals within the neurogenic niche. In this review, we summarize both classes of regulatory factors involved in distinct stages of adult neurogenesis, including proliferation and lineage differentiation of NSCs, migration of neuroblasts and integration of newborn neurons. A full understanding of the wide variety of signaling pathways will ultimately provide precise targets for therapeutic applications.

Figure 1

Neurogenesis in the adult brain. (a) Adult NSCs are primarily located in two germinal zones of the brain: the SVZ of the lateral ventricles and the SGZ of hippocampal DG. (b) A subset of relatively quiescent GFAP+ radial cells (type B cells) in the SVZ has the potential to serve as adult NSCs and generate rapidly dividing, transit-amplifying nonradial NSCs (type C cells), which in turn give rise to neuroblasts (type A cells) that migrate through the RMS toward the OB. (c) In the adult SGZ, a population of GFAP+ Sox2+ radial cells corresponds to quiescent NSCs (type 1 cells). They coexist with actively proliferating, GFAP- Sox2+ nonradial NSCs (type 2 cells) that generate both astrocytes and neuroblasts. Neuroblasts then migrate into the granule cell layer and mature into neurons.

Figure 2

Factors regulating the functional integration of newborn neurons. (a) Critical factors in the OB modulate survival, dendritic arborization, and maturation of newborn neurons. Migrating neuroblasts express NMDAR and receive glutamate signaling from astrocytes, which is crucial to neuroblast survival. (b) Critical factors in the SGZ influence the survival, dendritic arborization, and synaptic plasticity and integration of newborn neurons.