Grant: $264,678 - National Institutes of Health - Sep. 25, 2009
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Award Description: This application addresses broad Challenge Area (15) Translational Science, and the specific Challenge Topic, 15-NS-106: Identifying mechanisms that underlie nervous system development and function. This Challenge solicits mechanistic studies that elucidate principles of nervous system formation, as well as analyses of how normal mechanisms are perturbed in neurological disease. Spina bifida is one of the most common structural malformations in man; despite its high mortality and morbidity, the etiological causes of spina bifida remain poorly understood. We propose a mechanistic analysis of the causes of lumbar spina bifida in Noggin mutant mice. In contrast to virtually all other mouse strains with neural tube defects, the spina bifida phenotype in Noggin does not occur through a failure of the dorsal neural folds to close into a tube. Rather, a day or so after closure the lumbar spinal cord reopens dorsally in isolated regions along the midline. This results in a lumbar spina bifida phenotype. This mutant represents a novel mouse model for an unexplored mechanism of spina bifida that is likely to be more relevant to pathogenesis of some human cases of spina bifida than models in which the neural tube fails to close. We use tissue-specific gene ablation to determine the individual tissue requirements Noggin for maintenance of neurulation. Our preliminary data indicate that Noggin promotes adhesion of neural tube cells to cell adhesion molecules such as N-cadherin. Our overall hypothesis is that Noggin is required in the closed seam along the dorsal neural tube for maintenance of closure. We test this as well as alternative models, and evaluate downstream molecular and cellular pathways.
Project Description: See Award Description
Jobs Summary: N/A (Total jobs reported: 0)
Project Status: Not Started
This award's data was last updated on Sep. 25, 2009. Help expand these official descriptions using the wiki below.