Afadin Signaling at the Spinal Neuroepithelium Regulates Central Canal Formation and Gait Selection

Afadin, a scaffold protein controlling the activity of the nectin family of cell adhesion molecules, regulates important morphogenetic processes during development. In the central nervous system, afadin has critical roles in neuronal migration, axonal elongation, and synapse formation. Here we examine the role of afadin in development of spinal motor circuits. Afadin elimination in motor neuron progenitors results in striking locomotor behavior: left-right limb alternation is substituted by synchronous activation, characteristic of bound gait. We find that afadin function at the neuroepithelium is required for structural organization of the spinal midline and central canal morphogenesis. Perturbation of afadin results in formation of two central canals, aberrant contralateral wiring of different classes of spinal premotor interneurons, and loss of left-right limb alternation, highlighting important developmental principles controlling the assembly of spinal motor circuits.