Muscle-derived Cues are Required to Specify Proprioceptor Pool Identity

The formation of spinal sensory-motor circuits requires the diversification of proprioceptive sensory neurons (pSNs). During embryonic development, pSNs acquire molecular identities aligned with the limb muscle that they supply, but the extent of pSN "pool" diversity and how it is established are poorly understood. We find that the gene v-set transmembrane domain-2b (vstm2b) is preferentially expressed in pSN pools supplying dorsal limb muscle targets along the proximodistal extent of the limb. Genetic removal of muscle precursor cells from the developing limb greatly reduces the number of pSNs expressing vstm2b, demonstrating a requirement for limb muscle in specifying pSN pool identity. Comparison of dorsal and ventral muscle precursors identifies spatially restricted expression of the genes lumican (lum), decorin (dcn), and BMP binding endothelial regulator (bmper), demonstrating that dorsal and ventral muscle groups possess distinct molecular identities early in embryonic development. Together, these findings show that limb muscle is required for the specification of pSN pool identity and define early molecular correlates of dorsoventral muscle identity that are positioned to drive neuronal diversity.