Vertebrate Neurogenesis: Cell Polarity

Flavio R Zolessi, Universidad de la República, Montevideo, Uruguay

Published online: September 2009

DOI: 10.1002/9780470015902.a0000826.pub2

During development, neurons are formed from epithelial cells that, after proliferation and cell fate decisions, must undergo a series of transitions in polarity to achieve the differentiated state. The fate of neural progenitors greatly depends on the interplay between cell cycle and neuroepithelial polarity. In this respect, two main processes appear to influence neurogenesis: (a) the asymmetrical inheritance of apical or basal compartments during the last cell division and (b) the interkinetic nuclear migration through gradients of signalling molecules. After a neuron is born, the differentiation process starts with a downregulation of epithelial polarity, followed by cell detachment and migration and the final acquisition of a neuronal morphology. All these transitions are based on extremely conserved molecular mechanisms, including polarity protein complexes and small GTPases. However, some important variations have been observed in different neuronal types and experimental conditions, which might represent a tip for the neuronal type differentiation iceberg.

Key concepts:

  • Origin of neurons in the central nervous system of the vertebrates.
  • Cellular organization of the primordium of the central nervous system.
  • Importance of cell divisions in the development of the central nervous system.
  • Relationship between cell polarity and the generation of neurons.
  • Symmetrical and asymmetrical cell divisions and their role in cell fate determination in the central nervous system.
  • Cell polarity and maintenance of neural progenitors.
  • Cell polarity and neuronal migration.
  • Cell polarity and neuronal differentiation.
  • Morphological transitions that lead to neuronal differentiation.
  • Distinction between cell polarity and orientation in neuronal differentiation.

Keywords: neuroepithelium; neural progenitor; asymmetric cell division; neuronal migration; neuronal polarity

Figure 1. Not an easy task: how to make an epithelial cell into a neuron. Neuroepithelial cells, the progenitors of neurons, show a typical epithelial polarity, as they have an apical membrane separate from the basolateral membrane, apical specializations such as a primary cilium and adhesion complexes, and contact a basal lamina at the opposite side. All the cells of the neuroepithelium are oriented parallel to each other. Neurons are also polarized, but in a different way. The two major cell domains are the axonal and somato-dendritic compartments, which are specialized for a different organization: cells orient serially to each other. Neurons do not usually come into contact with any of the tissular surfaces.
Figure 2. Interkinetic nuclear migration and neurogenesis. Neuroepithelial cells can be tightly packed thanks to the particular ability to move their nuclei alternately between the apical and basal side of the tissue. This movement is synchronized by a natural clock: the cell cycle. However, not all the cells appear to move in the same way. Evidence discussed in the article (Baye and Link, 2007) suggest that cells that move their nuclei further basally during S phase, will undergo a neurogenic division after the next M phase. It might be possible that asymmetrically distributed signals along the apical–basal axis of the neuroepithelium are sensed by the nuclei as they migrate up and down, and are responsible for the cell decision to either stay as a dividing progenitor, or to embark in a neurogenic division. The receptor Notch, which mediates an antineurogenic signal, appears as an important candidate for this role, as suggested by current evidence (Del Bene et al., 2008).
Figure 3. The easy way: neuroepithelial–neuronal transition in the retina. (a) In the retina all progenitors are neuroepithelial cells, and the basal-most neurons (retinal ganglion cells) do not have to travel long distances to reach their final destination. Once the progenitor cell undergoes a neurogenic division, one (or both) of the daughter cells will extend to the basal surface and the nucleus will simply translocate down this basal process. When the nucleus is close to its final position, the apical process will detach, bringing at its tip components of the apical end foot: cell adhesion-related proteins and the centrosome. Neuronal differentiation (in particular, axonogenesis) will start as the cell gradually loses its epithelial polarity. For a short period of time, these neuroblasts look like an epithelial cell forming an axon at the opposite side of its apical domain. (b and c) In vivo time-lapse observations of the developing zebrafish retina supporting this model (Zolessi et al., 2006). Retinal ganglion cells are early labelled by red fluorescent protein (RFP) expression under the control of a specific promoter (from the transcription factor ATH5 gene), and the apical adhesion complex and centrosome are labelled with green fluorescent protein (GFP) fused to PAR3 and Centrin, respectively. Blue arrowhead, tip of the apical process; pink arrowhead, tip of the growing axon.
Figure 4. The hard way: neurogenesis in the cerebral cortex. The cortex is drawn here ‘upside-down’ with respect to the most common way of representing it, to make it more comparable to an epithelium, which is always shown with the apical side up. According to a current model of neurogenesis in the mammalian cortex, at some point in development the neuroepithelium splits in two, giving rise to two types of neural progenitors, radial glial cells and basal progenitors. Radial glial cells remain with their bodies close to the ventricle, in the ventricular zone. They mostly divide vertically. Path A shows a symmetric, proliferative, division. Paths B and C show different possible types of asymmetrical (although vertical) divisions, in which one daughter cell stays as a progenitor whereas the other one differentiates. The inheritance of the basal process by the differentiating cell determines the way of basal migration: cell locomotion (B) or nucleus translocation (C). Basal progenitors, however, detach from the apical surface of the neuroepithelium and form a new proliferative layer: the subventricular zone. They mostly divide symmetrically, giving rise to two differentiating daughter cells, and they very often show horizontal planes of cleavage (path D). When the migrating neuroblasts are going to differentiate as a pyramidal cell, they will grow their axons opposite to the direction of migration, leaving them behind as they move basally. They might even momentarily stop around the subventricular zone to initiate axon outgrowth, transiently directing their centrosome towards the base of the forming axon and changing their overall morphology. After the axon is formed, they will again direct the centrosome basally and resume migration.
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Related Sub-Topics:

Neurons | Nervous System Development | Intracellular and Extracellular Signalling | Growth and Synthesis | Genes, Molecules and Cellular Processes | Development of Vertebrate Nervous System | Cell Differentiation and Stem Cells
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Article Title: Vertebrate Neurogenesis: Cell Polarity
 
How to Cite close
Zolessi, Flavio R(Sep 2009) Vertebrate Neurogenesis: Cell Polarity. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000826.pub2]