The Adenomatous Polyposis Coli Protein Is an Essential Regulator of Radial Glial Polarity and Construction of the Cerebral Cortex

Radial glia are highly polarized cells that serve as neuronal progenitors and as scaffolds for neuronal migration during construction of the cerebral cortex. How radial glial cells establish and maintain their morphological polarity is unknown. Using conditional gene targeting in mice, we demonstrat...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2009-01, Vol.61 (1), p.42-56
Main Authors: Yokota, Yukako, Kim, Woo-Yang, Chen, Youjun, Wang, Xinshuo, Stanco, Amelia, Komuro, Yutaro, Snider, William, Anton, E.S.
Format: Article
Language:English
Subjects:
Adenomatous Polyposis Coli Protein - genetics
Adenomatous Polyposis Coli Protein - metabolism
Animals
Axonogenesis
beta Catenin - genetics
beta Catenin - metabolism
Cell Movement - physiology
Cell Polarity
Cell Proliferation
CELLBIO
Cerebral Cortex - cytology
Cerebral Cortex - embryology
DEVBIO
Intermediate Filament Proteins - genetics
Intermediate Filament Proteins - metabolism
Mice
Mice, Knockout
Microtubules - metabolism
Migration
MOLNEURO
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Nestin
Neuregulin-1 - genetics
Neuregulin-1 - metabolism
Neurogenesis
Neurogenesis - physiology
Neuroglia - cytology
Neuroglia - physiology
Neurons
Proteins
Regulation
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Summary:Radial glia are highly polarized cells that serve as neuronal progenitors and as scaffolds for neuronal migration during construction of the cerebral cortex. How radial glial cells establish and maintain their morphological polarity is unknown. Using conditional gene targeting in mice, we demonstrate that adenomatous polyposis coli ( APC) serves an essential function in the maintenance of polarized radial glial scaffold during brain development. In the absence of APC, radial glial cells lose their polarity and responsiveness to the extracellular polarity maintenance cues, such as neuregulin-1. Elimination of APC further leads to marked instability of the radial glial microtubule cytoskeleton. The resultant changes in radial glial function and loss of APC in radial glial progeny lead to defective generation and migration of cortical neurons, severely disrupted cortical layer formation, and aberrant axonal tract development. Thus, APC is an essential regulator of radial glial polarity and is critical for the construction of cerebral cortex in mammals.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2008.10.053