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HOMEODOMAIN PROTEIN AND CELL TYPE SPECIFICITY

$50,000R01FY2000NSNIH

Emory University, Atlanta GA

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Abstract

The present work is part of a general effort to determine the role of homeobox genes in the development and maintenance of neuronal specificity in the central nervous system. A growing number of studies have demonstrated specific defects in brain and spinal cord, and in a number of non-neuronal tissues, when homeobox genes have been disrupted during development. Although the CNS defects resulting from homeobox disruption are typically described in terms of particular anatomical structures or brain regions, the defects must ultimately reside in alterations of the phenotype of individual neurons, and further, result from the altered expression of particular structural genes. Homeobox genes are commonly regarded as developmental genes. Nonetheless, some continue expression into adulthood, and it is therefore speculated that they have a role in maintaining the integrity of neuronal structure, connectivity, or function. We use invertebrate models to test the effects of different patterns of homeodomain gene expression during defined times of embryogenesis and monitor the changes with a battery of cell-specific markers. We wish to determine whether cell types are altered, and whether there are other effects on formation of neuronal circuits.

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