The genus Aspergillus encompasses the most common fungi in the environment. Of all the aspergilli, Aspergillus nidulans is by far the most thoroughly studied member of this genus. The long-term objective of this project is to understand signaling mechanisms controlling multicellular sexual development in this model filamentous fungus. The presence of both asexual and sexual reproductive programs is a unique property of A. nidulans. However, signaling mechanisms mediating fruiting body formation from vegetatively growing hyphae are largely unknown. To better understand signal transduction in A. nidulans, nine genes (gprA ~ gprI) predicted to encode putative GPCRs have been identified in the A. nidulans genome and deletion mutations for six of them have been made. Phenotypic and genetic analyses lead to the hypothesis that GprA and GprB mediate signaling for activation of sexual development whereas GprD-mediated signaling is required for negatively controlling sexual development, which in turn confers proper vegetative growth. Specific aims of this project are to: 1) Dissect complex transcriptional regulation of GPCRs and examine molecular events responding to GPCR signaling; 2) Investigate the molecular basis of the negative relationship between stress and sexual development through GPCR expression; and 3) Examine expression and localization of the three GPCRs by reporter labeling. Outcomes of the project should fill critical research gaps regarding sexual development and GPCR-mediated signal transduction in the model filamentous fungus A. nidulans and enhance the knowledge on how a eukaryotic organism coordinates differentiation through balanced activities of two antagonistic GPCR mediated signaling cascades. The project will in turn provide new information and materials for undergraduate and graduate education in developmental biology, genetics and signal transduction in under-studied filamentous fungi. Understanding the GPCR-mediated regulation of development in A. nidulans will provide insight to control both beneficial and detrimental properties of medically, agriculturally or industrially important aspergilli.