A Hox code defines spinocerebellar neuron subtype regionalisation

Abstract

Coordinated body movement requires the integration of many sensory inputs. This includes 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 cell 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 knock-in mice, neuronal tracing and in situ hybridisation, we identify widespread expression of Hox cluster genes, including both protein-coding genes and microRNAs, 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 regionalisation. Specifically, we show that Hoxc9 function is required in most, but not all, cells of the major thoracic spinocerebellar column, Clarkes column, revealing heterogeneity reliant on Hox signatures.