9507857 Moses The Epidermal Growth Factor Receptor (EGFR) is a cell-surface protein that acts to carry signals from outside the cell into its interior. One of the molecules that binds to the EGFR, on the outside of the cell, is Transforming Growth Factor-alpha (TGF-alpha). Such signals are then used to regulate cell division and growth, and are necessary for normal development. For these reasons the EGFR, and the other steps in its pathway are the objects of intense study, and much is known about the molecular events that follow activation of the EGFR. Unfortunately, little is known of how the signals that act on the EGFR are regulated (such as TGF-alpha): the genes that control TGF-alpha are unknown. This is due, in large part, to the great expense and time needed to do genetic experiments in vertebrate animals. This research will use the economy and power of invertebrate genetics to overcome these difficulties to search for the genes that control TGF-alpha. Invertebrate homologs of TGF-alpha and the EGFR function in the development of the compound eye. Some mutations in the invertebrate EGFR affect the number and spacing of developing eye facets. Mutations in an invertebrate homolog of TGF-alpha (called spitz) also affect compound eye development. Recent data suggest that spitz function is required in the founding cell of the developing facet, and in the absence of spitz function, the founding cell cannot induce the differentiation of its neighbors, and facet development is aborted. The immediate objectives for this research project are to study early spitz mutant eye defects by histological examination, make antibodies to spitz protein to study its expression in the developing eye, make heat-sensitive mutations of invertebrate EGFR, to study its activity over time and, finally, to search for other genes that regulate the spitz signal. The results of these studies will provide fundamental information concerning the mechanisms by which extracellular signalling molecules regulate the growth and development of the nervous system.
