Epidermis-Derived Semaphorin Promotes Dendrite Self-Avoidance by Regulating Dendrite-Substrate Adhesion in Drosophila Sensory Neurons

•Sema-2b/PlexB signaling confines dendrites in a 2D space•Sema-2b is secreted from the epidermis and functions through PlexB in neurons•Sema-2b/PlexB signaling regulates Tricornered kinase activity in vivo•An integrin β subunit associates with PlexB receptor

SummaryPrecise patterning of dendritic arbors is critical for the wiring and function of neural circuits. Dendrite-extracellular matrix (ECM) adhesion ensures that the dendrites of Drosophila dendritic arborization (da) sensory neurons are properly restricted in a 2D space, and thereby facilitates contact-mediated dendritic self-avoidance and tiling. However, the mechanisms regulating dendrite-ECM adhesion in vivo are poorly understood. Here, we show that mutations in the semaphorin ligand sema-2b lead to a dramatic increase in self-crossing of dendrites due to defects in dendrite-ECM adhesion, resulting in a failure to confine dendrites to a 2D plane. Furthermore, we find that Sema-2b is secreted from the epidermis and signals through the Plexin B receptor in neighboring neurons. Importantly, we find that Sema-2b/PlexB genetically and physically interacts with TORC2 complex, Tricornered (Trc) kinase, and integrins. These results reveal a novel role for semaphorins in dendrite patterning and illustrate how epidermal-derived cues regulate neural circuit assembly.