This proposal outlines a series of experiments designed to test and refine our understanding of the mechanisms by which the developing nervous system is precisely patterned. Such precision is essential to the normal functioning of the brain; the means by which such patterning arises is essential to both our understanding of normal fetal development, and for developing therapies for the recovery from disease and injury-induced trauma to the nervous system. The ability of researchers to experimentally analyze brain development in vertebrates, however, is limited by the complexity of the vertebrate nervous system and difficulties making appropriate experimental manipulations. This proposal therefore outlines an ongoing series of experiments which examine the patterned development of the peripheral nervous system in the wing of the fruitfly, Drosophila melanogaster. In the fruitfly wing, the individual elements of the PNS arise in an extremely stereotyped fashion from a single epithelial sheet. The relative simplicity of the system and the availability of a number of molecular and genetic tools make it very favorable for experimental analyses. We will use a combination of genetic, molecular, and immunohistological techniques to analyze the molecular basis of this stereotypy, concentrating especially on the sensory organs that arise along the anterior wing margin. Our analysis includes testing the roles of a number of known genes and cell signalling pathways, and continuing a search for novel genes critical to the patterning process.
Our specific aims are to: 1. Examine the mechanisms underlying the formation of the dorsoventral compartment boundary. 2. Examine the role of the apterous boundary in localizing margin-specific gene expression; 3. Test the role of the margin-specific scalloped transcription factor in margin formation. 4. Test the role of the Notch signalling pathway in inducing margin wingless expression and neuronal development; 5. Examine the mechanisms by which wg can refine its domain of expression. 6) Examine the development and refinement of neural regions; 7) Screen for and characterize novel patterning genes using enhancer traps and the FLP-FRT Fl screening method.
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