Heterotrimeric G proteins are important bi-molecular switches that transmit signals from a diverse array of membrane receptors for neurotransmitters, hormones and extracellular morphogens to activate downstream intracellular signaling pathways. Members of the G?12/13 family are particularly important during embryonic development as they are essential for the development of the circulatory system and are required for embryonic angiogenesis. The goal of this proposal is to understand how Ric-8 participates in signaling in the G?12/13 pathway. We will use the Drosophila gastrulation pathway as a model system to study Ric-8 to take advantage of the powerful cell biological tools and rich understanding of the G?12/13 signaling pathway in flies. In this proposal we will 1) Conduct a structure-function study of Ric-8 within the context of G?12/13 signaling; and 2) Identify novel proteins that are required for regulating Ric-8 activity in Drosophila. Given the hih degree of conservation of these pathways between flies and humans, these studies will provide understanding of the regulation of G?12/13 protein signaling during vascular development and will identify novel molecules with potential therapeutic importance in the regulation of angiogenesis.