Drospondin, a novel glial-secreted glycoprotein, controls the development and function of theDrosophilanervous system

Abstract

Reelin is a secreted glycoprotein with roles in the development of the mammalian hippocampus and cerebral cortex. This vertebrate signaling molecule also contributes to adult brain function. Mammalian Reelin increases the complexity ofDrosophilaMushroom Body (MB) neurites, an effect mediated by LpR1 and LpR2, the orthologs of mammalian Reelin receptors. Paradoxically, to date, no Reelin ortholog has been described inDrosophila. Here, we report that the protein product of the uncharacterizedDrosophilaCG17739 gene, named Drospondin, shares sequence homology with vertebrate F-spondin and Reelin. We show that Drospondin is expressed in glial cells and is crucial for MB development. Our results also show that Drospondin interacts genetically with LpRs and that human Reelin rescues structural defects in Drospondin-deficient flies. Furthermore, Drospondin-deficient flies exhibit altered sleep homeostasis, locomotion, and social behaviors. Our results reveal that flies express a functional homolog of mammalian Reelin that controls the development and function of theDrosophilanervous system.