During brain development, cell proliferation, differentiation, and death must be properly controlled, and abnormalities in these processes are implicated in human neurological diseases, including microcephaly, schizophrenia, and cortical malformations. One protein that has been shown to regulate proliferation, differentiation, and death within the developing cortex is beta-catenin. Beta-catenin is a unique protein with a dual role: it functions in both cell-cell adhesion and as an important messenger in the canonical Wnt signaling cascade. We propose to shed further light on the role of beta-catenin in cortical development by selectively interfering with beta-catenin signaling within neural precursors in vivo, without disrupting a-catenin's role in adhesion. Our proposal is designed the following questions: (1) Will the loss of a-catenin signaling influence cell fate choices made by multipotent neural precursors? (2) Does beta-catenin signaling regulate neural precursor number by altering the rate of neural precursor proliferation, differentiation, or death? and (3) How does beta-catenin signaling regulate the balance between neural precursor proliferation and differentiation during early cortical development, prior to neurogenesis?
| Zhang, Jianing; Woodhead, Gregory J; Swaminathan, Sruthi K et al. (2010) Cortical neural precursors inhibit their own differentiation via N-cadherin maintenance of beta-catenin signaling. Dev Cell 18:472-9 |
| Woodhead, Gregory J; Mutch, Christopher A; Olson, Eric C et al. (2006) Cell-autonomous beta-catenin signaling regulates cortical precursor proliferation. J Neurosci 26:12620-30 |
