a-catenin is a unique protein with a dual role; it functions as both a key cytoskeletal component and as an important messenger in the Wnt signaling cascade. Beta-catenin has been implicated in numerous processes in normal development, carcinogenesis and disease. Previous work by our lab and others has shown that beta-catenin plays an important role in the development of the mouse neocortex. We propose to further the understanding of beta-catenin's role in the embryonic cortex using loss of function experiments designed to address the following questions: (1) Will the loss of beta-catenin change the fraction of neural precursor cells that exit the cell cycle? (2) What are the relative contributions of beta-catenin adhesion and signaling in neural precursors? We plan to answer these questions using a novel approach in which beta- catenin is deleted from only a small fraction of neural precursor cells. This will allow us to study precursor cells lacking beta-catenin in the context of a wild-type cortex, enabling us to draw conclusions about the cell- autonomous effects of the loss of beta-catenin.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30NS051864-03
Application #
7487861
Study Section
Special Emphasis Panel (ZNS1-SRB-M (34))
Program Officer
Riddle, Robert D
Project Start
2006-09-01
Project End
2010-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
3
Fiscal Year
2008
Total Cost
$57,427
Indirect Cost
Name
Northwestern University at Chicago
Department
Pathology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Mutch, Christopher A; Talbott, Jason F; Gean, Alisa (2016) Imaging Evaluation of Acute Traumatic Brain Injury. Neurosurg Clin N Am 27:409-39
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
Mutch, Christopher A; Schulte, Jessica D; Olson, Eric et al. (2010) Beta-catenin signaling negatively regulates intermediate progenitor population numbers in the developing cortex. PLoS One 5:e12376
Mutch, Christopher A; Funatsu, Nobuo; Monuki, Edwin S et al. (2009) Beta-catenin signaling levels in progenitors influence the laminar cell fates of projection neurons. J Neurosci 29:13710-9