Patronin facilitates neurite remodeling via epithelial-to-neuronal signaling

During development, the formation of precise neuronal connections and the refinement of neural circuits involves neurite pruning, a process that eliminates superfluous axons and dendrites without losing their parental cells. In Drosophila, the larval dendrites of class IV dendritic arborization (C4da) sensory neurons are selectively removed during development. Epidermal cells are known to be the primary phagocytes in the clearance of pruned and injured dendrites of Drosophila sensory neurons. However, its potential to act as a microenvironment that transmits signaling to facilitate dendritic pruning prior to performing phagocytosis is ambiguous. Here, we show that epithelium downregulation of Patronin, a conserved microtubule (MT) minus-end-binding protein, leads to dendrite pruning deficiency of C4da neurons. Mechanistically, Patronin compromises Flamingo, an adhesion GPCR, in the epithelium, maintaining normal function of neuronal Flamingo and facilitating dendritic breakage at the proximal region of C4da neuron soma, implying that epithelium may promote dendritic pruning through an intercellular mechanism, earlier than the execution of their phagocytic function. Furthermore, we also find that neuronal Flamingo represses the Drosophila Glycogen Synthase Kinase 3β (GSK3β) homolog Shaggy (Sgg) in dendrite remodeling. Collectively, these results demonstrate a novel epidermal-derived mechanism in promoting dendritic pruning, with the expectation of understanding the microenvironmental role of epithelial cells from a new perspective.