Sonic hedgehog is required for the induction of ventral cell types in the neural tube, and in recent years for rapid progress has been made in understanding the signaling pathway for sonic hedgehog. Using Xenopus laevis as a model, the Principal Investigator's groups has shown that Gli genes, which encode zinc finger transcription factors with transient and graded expression in the neural plate or neural tube, are involved in this process. Specifically, Gli1 has been found to be necessary and sufficient for floor plate and ventral neuronal differentiation, whereas Gli2 and Gli3 appear to antagonize the effect of Gli1. In further studies of the roles of Gli genes in sonic hedgehog signaling and development of the neural tube, the Principal Investigator proposes several important and ambitious studies. He proposed to analyze the tissue and cellular localization of the Gli1 gene products, to carry out a structure/function analysis of gli proteins using site- directed mutagenesis, to make Gli1 or Gli3 transgenic mice as a natural extension of the frog studies, to further analyze the antagonize Gli1 function in the frogs, and finally to determine if Gli3 is required for dorsal neural tube cell determination.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
3R01NS037352-02S1
Application #
6070002
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Finkelstein, Robert
Project Start
1998-02-20
Project End
2003-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
New York University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10016
Ruiz i Altaba, Ariel; Mas, Christophe; Stecca, Barbara (2007) The Gli code: an information nexus regulating cell fate, stemness and cancer. Trends Cell Biol 17:438-47
Clement, Virginie; Sanchez, Pilar; de Tribolet, Nicolas et al. (2007) HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol 17:165-72
Nguyen, Van; Chokas, Ann L; Stecca, Barbara et al. (2005) Cooperative requirement of the Gli proteins in neurogenesis. Development 132:3267-79
Sanchez, Pilar; Ruiz i Altaba, Ariel (2005) In vivo inhibition of endogenous brain tumors through systemic interference of Hedgehog signaling in mice. Mech Dev 122:223-30
Palma, Veronica; Lim, Daniel A; Dahmane, Nadia et al. (2005) Sonic hedgehog controls stem cell behavior in the postnatal and adult brain. Development 132:335-44
Sanchez, Pilar; Hernandez, Ana Maria; Stecca, Barbara et al. (2004) Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling. Proc Natl Acad Sci U S A 101:12561-6
Ruiz i Altaba, A (1999) Gli proteins encode context-dependent positive and negative functions: implications for development and disease. Development 126:3205-16
Ruiz i Altaba, A (1998) Combinatorial Gli gene function in floor plate and neuronal inductions by Sonic hedgehog. Development 125:2203-12
Liu, F; Massague, J; Ruiz i Altaba, A (1998) Carboxy-terminally truncated Gli3 proteins associate with Smads. Nat Genet 20:325-6