Neurogenesis in the Developing Mammalian Neocortex

Abstract

The neocortex is the evolutionarily newest and most complex part of the mammalian brain. The neurons of the neocortex are born from different neural stem and progenitor cells (for simplicity collectively referred to as progenitors) that reside in proliferative zones during embryonic development. During the neurogenic period, distinct populations of neural progenitors appear, each having specific molecular and cell biological characteristics. These characteristics and the environment of the neural progenitor are responsible for the self‐renewing or neurogenic potential of each neural progenitor type. The fate of daughter cells after neural progenitor division is determined by the mode of division, intrinsic factors such as transcription factors or regulatory ribonucleic acids (RNAs), and by extrinsic signals coming from the surrounding cells. This tight regulation controls the rate of production of neural progenitor types and neurons. The ratios of different progenitor types have a huge impact on the final number of neurons in the adult neocortex, and are partly responsible for vast differences in the brains of different mammals.

Key Concepts:

  • Neocortex is a part of the brain characteristic of mammals.

  • Neocortex is a six‐layered structure comprised of post‐mitotic neurons and glial cells.

  • Neocortical neurons are born from neural progenitor cells, mostly during embryonic development.

  • Neural progenitor cells can be classified into different populations based on molecular and cell‐biological features.

  • The molecular and cell‐biological features of neural progenitor cells influence their propensity to self‐renew or produce neurons.

  • Neural progenitor cells are under tight intrinsic and extrinsic control, in order to maintain the equilibrium between proliferative and neurogenic divisions.

  • The relative abundance of different progenitor populations influences the final number of neurons in the adult neocortex.

Keywords: mammals; neurogenesis; neocortex; neural progenitor; (a)symmetric division; evolution

Figure 1.

(a) Left: A schematic drawing of a developing rodent brain. Three main parts of the brain are visible. The dashed line indicates a sectioning plane (coronal), which is shown to the right. Right: A schematic drawing of a coronal section of a rodent brain at a mid‐neurogenesis stage. The dorsal telencephalon lies dorsally to the ventricles. The rectangle indicates the portion of a dorsal telencephalon which is magnified in (b) and (c). (b) A schematic drawing of the neuroepithelium before the onset of neurogenesis. The neuroepithelium is populated with neuroepithelial cells (NE cells, dark green nuclei). Note that the NE cells span the whole neuroepithelium and that the neuroepithelium is still not subdivided into germinal zones, but is comprised only of ventricular zone (VZ). The position of nuclei is correlated with the phase of the cell cycle they are in. During interkinetic nuclear migration (INM) the nuclei, after undergoing mitosis, translocate basally in G1. In S phase the nuclei are at their basal‐most position. During the G2 phase they move apically in order to undergo mitosis at the apical surface of the neuroepithelium. The pattern of INM remains the same as the neuroepithelium enlarges. (c) A schematic of the mid‐neurogenesis stage of an undefined mammal, drawn to present the morphology and position of different populations of progenitor cells. The cortical wall by this stage has divided into proliferative zones: VZ and the subventricular zone (SVZ), an intermediate zone (IZ) and the cortical plate (CP). The pattern of INM has not changed but, as the cortical wall thickened, the basal‐most position of the RG nuclei is situated on the border of VZ and SVZ.

Figure 2.

A magnified region of the apical‐most part of the neuroepithelium. Boxes in the upper panel indicate regions magnified in (a, b, c). (a) A symmetric division of an apical progenitor (AP). Pink region in the membrane line indicates apical membrane, surrounded by the apical complex. During cytokinesis, the cleavage takes place from the basal side, and the cleavage furrow ingresses perpendicularly towards the apical membrane. The symmetrical division implies that both daughter cells inherit the same amount of the apical membrane and cell constituents. (b) An asymmetrical division of an apical progenitor. If the cleavage furrow does not bisect the apical membrane, but either bypasses or descends into the apical complex, the division will be cell biologically asymmetric, as the daughter cells do not inherit equal amounts of the various cell constituents. The symmetric and asymmetric divisions, with regards to the apical region, are not always reflected in the fate of the daughter cells. (c) Apical‐most region of the VZ. The primary cilium (green) protrudes from the apical surface into the ventricular space where it receives signalling molecules. The primary cilium can also emerge from the basolateral side of the cell. Then it is termed basolateral cilium and is present on soon‐to‐delaminate cells (future basal progenitors). (d) A magnification of the apical complex (without primary cilium). The apical complex components shown include the N‐cadherin based adherens junctions (bordeaux), ZO‐1 (violet), the Par3/Par6/aPKC complex (turquoise) and the apical plasma membrane (pink).

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Further Reading

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Kelava, Iva, and Huttner, Wieland B(Nov 2012) Neurogenesis in the Developing Mammalian Neocortex. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022541]