This research program aims to study the developmental regulation and functions of specific neuropeptide gene expression. Neuropeptides play important, though poorly understood, roles in the control of the body, its development and its behavior. They are expressed in highly stereotyped patterns of neurons that represent small subsets of the total cellular complement. While a large body of work has described neuropeptide expression and function in vitro, much remains to be understood about such processes in vivo. This research utilizes the advanced techniques available in Drosophila for molecular-genetic analyses. The two long range goals of the work include (i) a better understanding of the mechanisms underlying neuropeptide gene expression by individual nerve cells. Clearly, events in vivo reflect complex responses to cellular interactions and to circulating factors that are difficult to emulate in vitro. The principle significance of proposed studies on the regulation of Drosophila FMRF amide gene expression is the use of in vivo techniques: germ line transformation methods are used to define and study sequence elements required for neuropeptide gene expression by specific identified neurons in their normal cellular environment. This information will contribute to specific knowledge of neuropeptide gene regulation, and to a more comprehensive understanding of mechanisms underlying neuronal development. The second long range goal is ii) an examination of the genetic defects that ensue as a consequence of mutations in the neuropeptide gene. Neuropeptides present a difficult problem for functional analysis because they contain a number of potential biologically active agents that may be working individually, or in concert. Traditional analyses of neuropeptide functions are pharmacological and often frustrated by the lack of specific antagonists by which to interrupt peptide action. In this regard, genetics should prove a useful complement to these other forms of experimental analysis for the study of neuropeptide function. It addresses gene function in its entirety, and thus considers the coordinate roles of distinct neuropeptides that are co-synthesized and co-released. This research program aims to recover specific loss-of and gain-of-function mutations, to study their effects, and to implicate defined peptide sequences with specific functions via re-introduction of gene sequences into mutant animals.
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