Figure 1. Neurogenesis in the adult rodent brain.

A sagital section of mouse brain shows the neurogenic microenvironments in the adult brain: the subventricular zone (SVZ) and the subgranular layer (SGL) of the dentate gyrus (DG). Stages of morphological and physiological development of neural stem cells (NSCs) in the SVZ (left) and SGL (right) are illustrated in inserts. Specifically, the SGL contains Type I NSCs, type II and type III cells which can be identified by distinct morphological and molecular markers. Type I have radial processes extending into the inner molecular layer. These cells express nestin, glial fibrillary acidic protein (GFAP), mammalian hairy and Enhancer-of-split homologues (Hes5), brain lipid binding protein (BLBP) and Sex determining region Y-box 1,2 (Sox1 and Sox2). This pool of NSCs stays relatively stable throughout life. Type II [neural progenitor cells (NPCs) or intermediate progenitors (IP)] have only short processes if any, and do not express GFAP. Type II cells may arise from type I cells. Type II cells can be divided to two subpopulations: (i) type IIa, which express Mash1 (Ascl1) as well as retaining expression of NSC markers such as Sox2, and (ii) type IIb cells, which are early-committed neuronal progenitors expressing the transcription factors Prospero homeobox protein 1 (Prox1), Neurogenic differentiation 1 (NeuroD1), as well as Doublecortin (Dcx). They continue to proliferate and may give rise to type III cells, which are migratory neuroblasts that express DCX and polysialated neural cell adhesion molecule (PSA-NCAM)-. After a limited number of cell divisions, type III cells exit the cell cycle and become mature granule neurons. Multiple signals in the local niche determine the fate of NSCs. These signals include: soluble factors (purple ovals) such as brain derived neurotrophic factor (BDNF), cell surface signals (yellow squares) such as Notch1, and extracellular matrix (ECM) factors such as laminin (pink triangles). Endothelial cells (EC) and astrocytes (AS) are thought to be supporting cells in the neurogenic niche, providing signals that are important for maintaining and mobilizing the NSC populations [2, 74]. In the SVZ, type B cells resemble SGL type I cells. They express GFAP, nestin, sox1, sox2, BLBP and the astrocyte-specific L-glutamate L-aspartate transporter (GLAST). They give rise to GFAP-negative transit-amplifying type C cells, which then give rise to type A cells. Type A are PSA-NCAM- and DCX-expressing neuroblasts that migrate radially on “glial tubes” in the rostral migratory stream (RMS) to layers in the olfactory bulb (OB) before terminal differentiation [107]. Abbreviations: cc, corpus collosum; hipp, hippocampus).