Members of the Hedgehog (Hh) family of signaling molecules mediate important developmental processes including patterning, morphogenesis of organs and cell specification. While the Hh pathway has been studied extensively, there is a lack of detailed understanding of the molecular and cellular mechanisms underlying this pathway. Genetic screens in zebrafish have identified several mutants that are defective in Hh signaling. The sonic-you (syu) locus encodes the zebrafish Sonic hedgehog and detour (dtr) and you-too (yot) loci encode the Gli1 and Gli2 zinc finger transcription factors, respectively. Mutations in these loci disrupt forebrain, spinal cord and somite development. A fourth mutant, chameleon (con), displays similar phenotypes as syu, dtr and yot, but the gene product has not been molecularly identified. Phenotypic analysis of con mutants suggests that con has a key function in Hh signaling during spinal cord development. This project has two specific aims: l) I will pursue the cloning of the con gene by using positional cloning, synteny conservation and candidate gene approaches. 2) The site of con action will be determined by genetic mosaic analysis by transplanting wildtype cells into con mutant embryos and vice versa, followed by assaying expression of nk2.2 in the spinal cord. To determine the epistatic relationship of con with members of the Hh signaling pathway, I will ectopically express Hh signaling components in con mutants and analyze marker gene expression in the spinal cord.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS011139-03
Application #
6629245
Study Section
Special Emphasis Panel (ZRG1-MDCN-6 (01))
Program Officer
Tagle, Danilo A
Project Start
2002-01-15
Project End
Budget Start
2003-01-15
Budget End
2004-01-14
Support Year
3
Fiscal Year
2003
Total Cost
$46,420
Indirect Cost
Name
New York University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016