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  • Review Article
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Spindle regulation in neural precursors of flies and mammals

Nature Reviews Neuroscience volume 8, pages 89–100 (2007)Cite this article

Key Points

  • Cleavage plane angle is a developmentally regulated property in mammalian neural progenitor cells. It is highly correlated with the production of different types of daughter cells and can be used to control the distribution of cell fate determinants.

  • Tumor suppressor proteins help regulate the asymmetric distribution of various proteins necessary for ganglion mother cell fate specification in the dividing Drosophila melanogaster neuroblast.

  • Asymmetrical inheritance of vertebrate numb homologues during neural progenitor cell division has important consequences for cell fate determination.

  • A conserved cassette of apically localized proteins helps to establish distinct apical and basal domains in D. melanogaster neuroblasts. The proteins also help to coordinate alignment of the mitotic spindle between these domains.

  • D. melanogaster partner of inscuteable (PINS) links spindle orientation to the apical protein domain and also mediates the establishment of spindle asymmetry. Mammalian homologs of PINS are involved in regulating spindle orientation with important implications for daughter cell fate.

  • The heterotrimeric G proteins transduce signals necessary for the control of spindle alignment in flies and mammals. Their cycle of activity is closely controlled by a number of regulatory proteins.

  • D. melanogaster mushroom body defect (MUD) and a mammalian protein that shares limited homology, nuclear mitotic apparatus (NUMA), serve as links between cortical proteins and the mitotic spindle, allowing them to coordinate.

  • The presence of adherens junctions in D. melanogaster neuroepithelial cells influences spindle orientation. Several animal models indicate that adherens junctions and associated polarity proteins might have important roles in determining division mode and the identity of mammalian neural progenitors.

Abstract

The mitotic spindle is the cellular scaffold that facilitates proper segregation of genetic material during cell division. Far from being static, the spindle is a dynamically regulated tool that can alter its size, shape and position during mitosis. Work in both insect and vertebrate systems has shown that regulation of this structure involves an array of highly conserved proteins. Moreover, it is now clear that tight regulation of the spindle during the process of neurogenesis is paramount to proper cell division and generation of the nervous system as a whole.

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Figure 1: Neural progenitor division and potential factors governing cell fate determination in the embryonic mammalian neocortex.
Figure 2: Neuroblast division in the Drosophila melanogaster embryo.
Figure 3: Neuroblast delamination, polarity establishment and division.
Figure 4: Potential models of spindle orientation in flies and mammals.
Figure 5: Adherens junctions and cell division.

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Acknowledgements

We would like to thank the following individuals for their comments and input during the writing of this manuscript: Z. Xie, R. Ayala, X. Ge and K. Sanada.

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Authors and Affiliations

  1. Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, RIKEN-MIT Neuroscience Research Center, Howard Hughes Medical Institute, Cambridge, Massachusetts, USA

    Joshua J. Buchman & Li-Huei Tsai

  2. Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA

    Joshua J. Buchman

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  1. Joshua J. Buchman
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Correspondence to Li-Huei Tsai.

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Glossary

Ventricular zone

(VZ). The proliferative region of the mammalian neocortex from which neurons arise. It is the most apical layer of the cortex. It lines the cerebral ventricles and sits directly below the subventricular zone.

Neuroepithelial cell

The main proliferative cell type of the early neocortex, which divides to expand the ventricular zone and gives rise to neurons and radial glial cells. Dividing cells of the retina and neural tube are also referred to as neuroepithelial cells.

Radial glia

The main neurogenic cell type found in the neocortical ventricular zone during the peak period of neurogenesis. These cells can divide asymmetrically to generate a neuron as well as another radial glial cell.

Basal progenitors

A class of progenitors which divide at positions basal to the ventricular surface. They usually divide only 1–2 times to produce terminally differentiated neurons. Unlike other neural progenitors, they do not maintain contact with the ventricular surface and lack overt polarity.

Cleavage plane

Refers to the orientation of the cleavage furrow generated during mitosis. The cleavage plane angle is perpendicular to the orientation of the spindle poles and approximately perpendicular to the plane across which two cells separate.

Horizontal cleavage

A mitotic division during which the mitotic spindle poles are oriented along the apicobasal axis, perpendicular to the luminal surface so that the cleavage furrow forms parallel to the luminal surface.

Vertical cleavage

A mitotic division during which the mitotic spindle poles are oriented parallel to the plane of the luminal surface so that the cleavage furrow forms perpendicular to the luminal surface.

Symmetric division

A mitotic division generating daughter cells with identical cell fates.

Asymmetric division

A mitotic division generating daughter cells with different cell fates.

Neurogenic division

Any division that produces a neuron. Terminal neurogenic divisions produce two neurons incapable of further division.

Tumour suppressor protein

A protein that functions to prevent tumour formation by any of a number of mechanisms, including preventing cell cycle re-entry or inducing apoptosis in cells harbouring DNA damage.

G-protein coupled receptor

(GPCR). Any of a family of seven transmembrane proteins that couple extracellular ligand binding to activation of intracellular G-protein signalling cascades. These proteins are involved in signalling processes as diverse as sensory perception, the inflammatory response and autonomic nervous system responses.

Guanine dissociation inhibitor

(GDI). A protein that acts to slow the spontaneous exchange of GDP for GTP on Gα proteins.

Guanine nucleotide exchange factor

(GEF). A protein that catalyses the dissociation of GDP from small Gα proteins to promote binding of GTP.

Regulator of G-protein signalling

(RGS). Any member of a family of proteins that contains an RGS-box domain and can accelerate the intrinsic GTP hydrolysis activity of small Gα proteins.

GTPase activating proteins

(GAP). Proteins, such as regulators of G-protein signalling, that can accelerate the intrinsic GTP hydrolysis activity of small Gα proteins.

Mushroom body

A paired neuropil structure found in the Drosophila melanogaster brain that functions in learning and memory.

Cadherins

A family of adherens junction component proteins that form calcium-dependent homotypic associations across cells to promote cell–cell adhesion and intercellular signalling.

αE-catenin

A member of the α-catenin family expressed in neural progenitor cells. α-Catenins are actin-binding proteins associated with adherens junctions.

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Buchman, J., Tsai, LH. Spindle regulation in neural precursors of flies and mammals. Nat Rev Neurosci 8, 89–100 (2007). https://doi.org/10.1038/nrn2058

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