Metamorphosis of the Drosophila brain involves pruning of many larval-specific dendrites and axons followed by outgrowth of adult-specific processes. From a genetic mosaic screen, we recovered two independent mutations that block neuronal remodeling in the mushroom bodies (MBs). These phenotypically indistinguishable mutations affect Baboon function, a Drosophila TGF-β/activin type I receptor, and dSmad2, its downstream transcriptional effector. We also show that Punt and Wit, two type II receptors, act redundantly in this process. In addition, knocking out dActivin around the mid-third instar stage interferes with remodeling. Binding of the insect steroid hormone ecdysone to distinct ecdysone receptor isoforms induces different metamorphic responses in various larval tissues. Interestingly, expression of the ecdysone receptor B1 isoform (EcR-B1) is reduced in activin pathway mutants, and restoring EcR-B1 expression significantly rescues remodeling defects. We conclude that the Drosophila Activin signaling pathway mediates neuronal remodeling in part by regulating EcR-B1 expression.
Bibliographical noteFunding Information:
We thank D. Andrew for the Df(1)Desi-S3 , N. Perrimon for the Df(1)hl-a , S. Robinow for UAS-EcR flies, the Bloomington Stock Center for other mutant flies, C. Thummel for anti-EcR antibodies, and P. ten Dike for anti P-Mad and anti P-Smad2 antibodies. We thank D. Montell, G. Robinson, and members of the Lee lab, especially C.T. Zugates, for comments on the manuscript. This work was supported by National Institutes of Health Grant NS42049 to T.L. T.L. is a Klingenstein fellow and a Sloan fellow, and M.B.O. is an associate investigator with the Howard Hughes Medical Institute.