All eukaryotic organisms have conserved a specific set of mechanisms for receiving and responding to extracellular signals. In most cases, these mechanisms depend on the presence of cell membrane receptors that act as signal discriminators. Such receptor systems mediate sensory transduction in the adult organism and are also employed to relay signals of developmental significance. The most ancient and diverse signalling system involves the use of a group of structurally related extracellular receptors that couple to intracellular second messenger generating systems by means of G proteins. Studies in simple organisms such as yeast point out the significance of this form of sensory transduction in mediating cell determination events during development.
The aim of our studies is to investigate to role of metazoan G protein coupled receptor systems in relaying signals of developmental consequence. For these studies, we will employ the fruit fly Drosophila as an experimental system because of the wealth of genetic and molecular tools it offers as well as the easy accessibility of well--described developmental stages. We will focus specifically on the role of G protein-coupled receptors that are expressed at the earliest stages of development. A Drosophila homolog of vertebrate tachykinin receptors and a novel receptor, both expressed early in development, have been identified. These receptors will allow us to test hypotheses concerning the participation of individual receptor systems in early and cell-specific developmental responses. In addition, we will continue to identify CDNAS encoding a limited number of receptors which we predict are expressed early in embryogenesis and may therefore participate in initial determination events. The expression of each receptor within the context of well characterized developmental pathways will be analyzed using tools such as specific antibodies. These studies will allow us to predict specific roles for each receptor in mediating early developmental events or the development of specific populations of cells. Using this framework, specific predictions will be tested by the manipulation of the expression of each receptor by genetic techniques. Using this system, we will be able, for the first time, assess the potential of individual G protein coupled receptor systems to mediate the transduction of developmentally important signals.
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