Neurogenesis during development of the vertebrate central nervous system

Abstract

During vertebrate development, a wide variety of cell types and tissues emerge from a single fertilized oocyte. One of these tissues, the central nervous system, contains many types of neurons and glial cells that were born during the period of embryonic and post-natal neuro- and gliogenesis. As to neurogenesis, neural progenitors initially divide symmetrically to expand their pool and switch to asymmetric neurogenic divisions at the onset of neurogenesis. This process involves various mechanisms involving intrinsic as well as extrinsic factors. Here, we discuss the recent advances and insights into regulation of neurogenesis in the developing vertebrate central nervous system. Topics include mechanisms of (a)symmetric cell division, transcriptional and epigenetic regulation, and signaling pathways, using mostly examples from the developing mammalian neocortex.

Figure 1

Schematic overview of neurogenesis in the embryonic vertebrate CNS. The principal types of NPCs with the progeny they produce are indicated by different colors. Additional NPC types that are typically found in mammalian neocortex are indicated in the box; note that only some of the possible daughter cell outcomes are depicted.

Figure 2

Division types of NPCs are determined by spindle orientation and inheritance of cell fate determinants. (A, B) Symmetric division yields two NPCs, whereas asymmetric NPC division yields one NPC daughter and one differentiating daughter cell. (C) Spindle orientation in symmetric versus asymmetric divisions is regulated by centrosomal protein and spindle orientation complexes in vertical and oblique divisions of vertebrate NPCs (left and middle) and horizontal neuroblast divisions in Drosophila. (D) Cell fate determinants may be equally (symmetric division, left) or unequally (middle, mouse; right, zebrafish) distributed between daughter cells. (E, F) Examples of asymmetries between daughter cells that were introduced by asymmetric inheritance of differently aged centrioles and ciliary membrane (E), and Par3 and Notch signaling components (F).

Figure 3

Environmental cues regulating NPC proliferation and differentiation. For details, see text.

Figure 4

Extracellular and intracellular factors affecting the balance between NPC proliferation versus differentiation. For details, see text. TF, transcription factor.