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 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.
Yokota
Yukako
Y
UNC Neuroscience Center and the Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Kim
Woo-Yang
WY
Chen
Youjun
Y
Wang
Xinshuo
X
Stanco
Amelia
A
Komuro
Yutaro
Y
Snider
William
W
Anton
E S
ES
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D016764:Cell Polarity; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology; D009457:Neuroglia / Q000166:cytology / Q000502:physiology; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D025601:Adenomatous Polyposis Coli Protein; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D020890:Neuregulin-1; D051176:beta Catenin