Columnar-Intrinsic Cues Shape Premotor Input Specificity in Locomotor Circuits

Abstract

Summary: 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. : 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. Keywords: spinal circuit, motor neuron, sensory neuron, Hox gene, neural development, transcription factor, locomotion