A Hox Code Defines Spinocerebellar Neuron Subtype Regionalization

Eamon Coughlan, Victoria C. Garside, Siew Fen Lisa Wong, Huazheng Liang, Dominik Kraus, Kajari Karmakar, Upasana Maheshwari, Filippo M. Rijli, James Bourne, Edwina McGlinn

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)2408-2421
Number of pages14
JournalCell Reports
Volume29
Issue number8
DOIs
Publication statusPublished - 19 Nov 2019

Keywords

  • Gdnf
  • Hox cluster
  • Hox gene
  • Hoxc9
  • microRNA
  • miR-196
  • proprioception
  • sensory neuron
  • spinal cord patterning
  • spinocerebellar

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