Wnts are extracellular signals known to regulate neurogenesis in regions associated with developmental diseases such as autism and schizophrenia, yet cell cycle mechanisms mediating these effects remain undefined.
We aim to study Wnt-3a's role in forebrain neurogenesis and G1 cell cycle machinery regulation in culture, and in vivo, as follows: l) Embryonic rat cortical cell cultures will be treated with media conditioned by fibroblasts transfected with Wnt-3a constructs. S-phase entry will be assessed by [3H]Thymidine incorporation, and characterized cellularly by bromodeoxyuridine labeling. 2) Wnt-3a's effects on cell cycle regulatory protein levels, including D and E cyclins, cyclin dependent kinases (CDKs), and CIP/KIP CDK inhibitors, will be measured by western blotting, and cyclin/CDK complex activity will be assessed by kinase assays. 3) Acute effects of Wnt-3a on proliferation and cell cycle regulation in vivo, will be determined using transuterine intracerebroventricular (ICV) injection. Sustained effects on neurogenesis will be assessed using GFP:Wnt-3a co-transfection by cell electroporation. Defining these mechanisms mediating Wnt signaling in brain development is critical to understanding and treating pervasive neurological diseases.

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 #
5F30NS048649-03
Application #
7086376
Study Section
Special Emphasis Panel (ZNS1-SRB-M (01))
Program Officer
Owens, David F
Project Start
2004-07-01
Project End
2008-10-31
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
3
Fiscal Year
2006
Total Cost
$28,965
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Neurosciences
Type
Schools of Medicine
DUNS #
617022384
City
Piscataway
State
NJ
Country
United States
Zip Code
08854
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Benayed, Rym; Gharani, Neda; Rossman, Ian et al. (2005) Support for the homeobox transcription factor gene ENGRAILED 2 as an autism spectrum disorder susceptibility locus. Am J Hum Genet 77:851-68