Cell body position of Drosophila Moonwalker Descending Neurons regulates locomotor circuit function

Both mammalian and invertebrate nervous systems contain densely packed neuronal cell bodies in stereotyped locations, which express cell surface molecules and gap junction proteins. An open question that has rarely been addressed is: What role does cell body position play in neuronal circuit function? Here we show that the four adult Drosophila Moonwalker Descending Neurons (MDNs), command neurons for backward locomotion, must maintain cell body contact to initiate backward walking. MDNs express the transcription factor Hunchback, which drives expression of the cell adhesion molecule Lar. Hunchback, Lar, and its ligand Dlp, promote MDN cell body clustering, which blocks initiation of backward walking. When the cell bodies are clustered, electrical synapses form between MDN cell bodies. The gap junction protein Innexin 8 (also known as Shaking B) maintains a more depolarized resting membrane potential and allows synchronous firing of MDNs. Together, these electrophysiological properties are necessary to initiate backward walking. These findings reveal a previously unappreciated role for cell body location, and the properties it mediates, in neural circuit function.