Centrosomes in Asymmetric Cell Division and Neocortical Development

Abstract

Centrosomes play crucial roles in the homeostasis and cell cycle progression of many different cell types, and neural stem and progenitor cells (NSPCs) are not the exception. In fact, NSPCs could be among the cell types where the functions and characteristics of centrosomes are most diverse and unique. From spindle orientation to subcellular organization to primary cilium formation and beyond, centrosome functions are intimately linked to the highly polarized and dynamic architecture of NSPCs in the cerebral neocortex. This leads us to argue that centrosomes are among the organelles that most influence the cytoarchitecture of NSPCs, which translates into a decisive influence in their proliferation, differentiation and tissue and organ formation properties.

Key Concepts

  • Centrosomes are crucial for the cell and tissue biology of neural stem and progenitor cells (NSPCs).
  • Centrosomes control symmetric vs. asymmetric cell division in NSPCs.
  • Many genes implicated in neurodevelopmental disorders, such as primary microcephaly, encode centrosome proteins.
  • Centrosomes also fulfil essential nonmitotic functions, such as primary cilium formation.
  • NSPC proliferation and differentiation are influenced in diverse ways by centrosomes.

Keywords: centrosomes; asymmetric cell division; spindle orientation; primary cilium; cell polarity; cell fate; neural stem cells; radial glia; neuroepithelial cells; cortical development; neural development; neocortex

Figure 1. Centrosomes and cilia during cortical development. Major neural stem and progenitors cell (NSPC) types (blue nuclei) through the cell cycle in the developing neocortex during mid neurogenesis. Apical progenitors (APs) extend processes to connect to both the apical (ventricular) surface and the basal lamina, below the meninges. They also connect to each other via an adherens junctions belt (green‐black) and their nuclei reside in the ventricular zone (VZ). In M‐phase (M), the centrosomes (red) nucleate, position and orient the mitotic spindle. In G1, the centrosomes become the basal body of the primary cilia (yellow) and remain apical, while the nucleus initiates interkinetic (or intermitotic) nuclear migration by moving basally. The Golgi apparatus (magenta) spreads along the apical process. In S‐phase (S), the AP nucleus resides basally during chromosome and centrosome duplication. In G2, the nucleus migrates apically for the next mitosis. In AP symmetric divisions, abundant astral microtubules maintaining a mostly horizontal AP spindle. In some AP asymmetric divisions, a ciliary membrane remnant can stay associated with the mother centriole. Other progenitors derived from APs delaminate and accumulate basally. In rodents, most are neurogenic basal intermediate progenitors (bIPs) that lose apicobasal polarity. Also present, especially in mammals with a large neocortex, are basal radial glia (bRG) that delaminate from the apical surface but can still have processes and proliferate. The spindles of both these types of basal progenitors are oriented more variably, with fewer astral microtubules. Neurons (green nuclei) generated by NSPCs migrate and accumulate basally. Cells and tissue are not drawn to scale, and the basal zones and neuronal layers are not shown in detail. Fading colours indicate tissue depth.
Figure 2. The centrosome cycle in apical radial glia (aRG) of the developing mammalian neocortex. DNA staining with DAPI (cyan) and actin staining with phalloidin (white), and indirect immunofluorescence for γ‐tubulin (green) and Arl13b (red) of sections of E14.5 mouse dorsolateral telencephalon. (a) Prophase, with the axoneme and membrane of the primary cilium (ARL13B, red) and the basal body (green) that is being internalised through the apical domain (arrowhead), the apical‐most part of the aRG membrane with low actin density (white) that is delimited by adherens junctions (not shown). (b) Metaphase, The centrosomes that were at the basal body are now the poles of the mitotic spindle (arrowheads). In some divisions, the mother centrosome can retain part of the ciliary membrane (left spindle pole). (c) Late telophase/G1, the centrioles are now again part of the growing primary cilia that begin to protrude from the apical membrane of each daughter cell (arrowheads). (d) Interphase, likely G2, with a mature primary cilium dipped in cerebrospinal fluid. The scale bar is 5 µm and marks the apical side of the tissue.
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Mora‐Bermúdez, Felipe, and Huttner, Wieland B(Sep 2018) Centrosomes in Asymmetric Cell Division and Neocortical Development. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021863]