dCORL is required for dSmad2 activation of Ecdysone Receptor expression in the Drosophila mushroom body. Stuart J. Newfeld¹, Michael Stinchfield¹, Kazumichi Shimizu², Mayu Arase³, Janine Quijano¹, Tetsuro Watabe³, Kohei Miyazono³, Norma T. Takaesu¹. 1) Sch Life Sci, Arizona State Univ, Tempe, AZ; 2) Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan; 3) Department of Molecular Pathology, University of Tokyo, Tokyo 113-0033, Japan.

   CORL proteins (fussel in humans) are related to Sno/Ski oncogenes but their developmental roles are unknown. We cloned dCORL and show its expression is restricted to distinct subsets of cells in the central nervous system. We generated a deletion of dCORL and noted that homozygous individuals rarely survive to adulthood. Df(4)dCORL adult escapers display mushroom body defects and Df(4)dCORL larvae are missing Ecdysone Receptor (EcR-B1) expression in mushroom body neurons. This is phenocopied in dCORL-RNAi and dSmad2-RNAi clones in wild type larvae. Further, constitutively active Baboon (Type I receptor upstream of dSmad2) cannot stimulate EcR-B1 mushroom body expression in Df(4)dCORL larvae demonstrating a formal requirement for dCORL in dSmad2 signaling. Studies of mCORL1 revealed that it binds specifically to Smad3. Overall the data suggest that dCORL facilitates dSmad2 activity upstream of EcR-B1 in the mushroom body. The conservation of neural expression and strong sequence homology of all CORL proteins suggests that this is a new family of Smad co-factors.