Spinal circuit regionalization diversifies motor output along the vertebrate body axis

ABSTRACT The evolution of the vertebrate limb-torso-limb body plan drove a diversification of motor behavior. How neural circuits are organized to generate distinct outputs across body regions, however, remains unknown. Here, we construct a cross-species, spatiotemporal atlas of spinal interneurons spanning the rostrocaudal and developmental axes of frogs and mice. We uncover a common framework of interneuron regionalization that mirrors each vertebrate’s body plan and arises through Hox-dependent regulation of rostrocaudal neurogenesis. Combining electrophysiology with computational modeling, we show that changing regional circuit composition is sufficient to respecify motor output. Together, these findings establish a causal link between developmental patterning, circuit architecture, and motor function, identifying interneuron regionalization as a fundamental organizational principle linking body-plan evolution to motor diversity.