Cell-autonomous beta-catenin signaling regulates cortical precursor proliferation.
Overexpression of beta-catenin, a protein that functions in both cell adhesion and signaling, causes expansion of the cerebral cortical precursor population and cortical surface area enlargement. Here, we find that focal elimination of beta-catenin from cortical neural precursors in vivo causes premature neuronal differentiation. Precursors within the cerebral cortical ventricular zone exhibit robust beta-catenin-mediated transcriptional activation, which is downregulated as cells exit the ventricular zone. Targeted inhibition of beta-catenin signaling during embryonic development causes cortical precursor cells to prematurely exit the cell cycle, differentiate into neurons, and migrate to the cortical plate. These results show that beta-catenin-mediated transcriptional activation functions in the decision of cortical ventricular zone precursors to proliferate or differentiate during development, and suggest that the cell-autonomous signaling activity of beta-catenin can control the production of cortical neurons and thus regulate cerebral cortical size.
Woodhead
Gregory J
GJ
Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Mutch
Christopher A
CA
Olson
Eric C
EC
Chenn
Anjen
A
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D005260:Female; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000502:physiology*
D051176:beta Catenin