The long-term objective of the proposed research is to understand the molecular mechanisms that control dendrite development in both Drosophila and vertebrates. flamingo (fmi), one of 12 genes that control dendrite development identified by genetic screen on 2nd chromosome (about 40% genes of the genome) in the Jan lab, is required for proper dendrite extension of multiple dendrite neurons in Drosophila. fmi encodes a non-classic type cadherin family member with seven- transmembrane domain, large extracellular and intracellular segments, and appears to be a receptor. The yeast two-hybrid system and genetic screening on 3rd chromosome will be used to identify and characterize molecular components of Fmi signaling pathway. Genetic screen on chromosome (40% genes of the genome) will also find additional genes that control dendrite development. The proposed research will advance our understanding molecular mechanisms that control dendrite development and potentially will improve the rationale for drug design, drug screen, disease diagnoses and disease treatment.