Our previous experiments, which represent the basis for this proposal, have shown that the cranial neural tube can regulate to form neural crest cells after ablation of the neural folds (Scherson et al. 1993). These experiments suggest that cranial neural tube cells have the potential to become neural crest cells. The goal of this proposal is to examine the cellular and molecular responses underlying the remarkable regulative ability of the neural tube to form neural crest. The proposed experiments will further characterize the effects of ablations to see if similar regulative ability occurs at all axial levels of the neural tube. In addition, we will examine whether other populations of cells, such as the ectodermal placodes, may contribute to neural crest cells when the endogenous neural crest is removed. To examine the molecular nature of the responses underlying this regulative ability, we will characterize the expression pattern after ablation of a variety of marker genes normally found in the dorsal neural tube or neural crest: inducing Slug, Wnt-3a, Pax-3 and some newly isolated genes. The goal is to elucidate which genes are up-regulated after ablation and in what sequence. Having identified candidate genes, we will inhibit their function using antisense oligonucleotides and retrovirally-mediated gene transfer. The effects of such gene """"""""knock-outs"""""""" on neural crest formation will help determine which genes are necessary for the regulative response. The experimental design will involve in vivo manipulation by neural fold ablation, coupled with cell marking techniques to identify the origin of neural crest populations, as well as in situ hybridization to look at their gene expression. Specific experiments will examine: 1. genes that are up-regulated in ventral neural tube cells after ablation of the neural folds. 2. regional differences in the regulative response of the neural tube along the neural axis. 3. the importance of inductive interactions between the neural tube and presumptive epidermis in neural crest formation from the ventral neural tube. 4. whether existing neural fold cells inhibit the regulative response of the neural tube. 5. possible contributions of ectodermal placodes to """"""""neural crest"""""""" derivatives after neural fold ablation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS034671-04
Application #
2750919
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Finkelstein, Robert
Project Start
1995-09-30
Project End
1999-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
California Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
078731668
City
Pasadena
State
CA
Country
United States
Zip Code
91125
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Selleck, M A; Garcia-Castro, M I; Artinger, K B et al. (1998) Effects of Shh and Noggin on neural crest formation demonstrate that BMP is required in the neural tube but not ectoderm. Development 125:4919-30

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