A Hox Code Defines Spinocerebellar Neuron Subtype Regionalization

Abstract

Summary: Coordinated movement requires the integration of many sensory inputs including proprioception, the sense of relative body position and force associated with movement. Proprioceptive information is relayed to the cerebellum via spinocerebellar neurons, located in the spinal cord within a number of major neuronal columns or as various scattered populations. Despite the importance of proprioception to fluid movement, a molecular understanding of spinocerebellar relay interneurons is only beginning to be explored, with limited knowledge of molecular heterogeneity within and between columns. Using fluorescent reporter mice, neuronal tracing, and in situ hybridization, we identify widespread expression of Hox cluster genes within spinocerebellar neurons. We reveal a “Hox code” based on axial level and individual spinocerebellar column, which, at cervico-thoracic levels, is essential for subtype regionalization. Specifically, we show that Hoxc9 function is required in most, but not all, cells of the thoracic spinocerebellar column, Clarke’s column, revealing heterogeneity reliant on Hox signatures. : Coughlan et al. utilize fluorescent reporter mice to characterize the projection patterns of embryonic and adult spinocerebellar neurons (SCNs). Within the spinal cord, axially restricted SCNs are delineated by their unique repertoire of posterior Hox-cluster gene expression, and a requirement for Hox function in SCN subtype regionalization is demonstrated. Keywords: Hox gene, Hox cluster, spinocerebellar, proprioception, sensory neuron, miR-196, Hoxc9, microRNA, Gdnf, spinal cord patterning