Columnar-Intrinsic Cues Shape Premotor Input Specificity in Locomotor Circuits

Control of movement relies on the ability of circuits within the spinal cord to establish connections with specific subtypes of motor neuron (MN). Although the pattern of output from locomotor networks can be influenced by MN position and identity, whether MNs exert an instructive role in shaping synaptic specificity within the spinal cord is unclear. We show that Hox transcription-factor-dependent programs in MNs are essential in establishing the central pattern of connectivity within the ventral spinal cord. Transformation of axially projecting MNs to a limb-level lateral motor column (LMC) fate, through mutation of the Hoxc9 gene, causes the central afferents of limb proprioceptive sensory neurons to target MNs connected to functionally inappropriate muscles. MN columnar identity also determines the pattern and distribution of inputs from multiple classes of premotor interneurons, indicating that MNs broadly influence circuit connectivity. These findings indicate that MN-intrinsic programs contribute to the initial architecture of locomotor circuits. [Display omitted] •MN columnar identity influences premotor input specificity in motor circuits•Loss of Hoxc9 disrupts sensory-motor matching in type Ia stretch reflex circuits•Premotor interneuron input pattern is shaped by MN topographic organization•MN-intrinsic programs contribute to locomotor circuit architecture Baek et al. show that Hox transcription-factor-dependent programs in motor neurons determine the specificity of presynaptic inputs from sensory neurons and interneurons. These findings indicate that motor neuron intrinsic programs play an instructive role in shaping the architecture of locomotor circuits.