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A Hox Code Defines Spinocerebellar Neuron Subtype Regionalization.

Eamon Coughlan1, Victoria C Garside1, Siew Fen Lisa Wong1

  • 1EMBL Australia, Australian Regenerative Medicine Institute, Monash University, Clayton, VIC 3800, Australia.

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|November 21, 2019
PubMed
Summary

Researchers discovered a "Hox code" in spinocerebellar neurons, crucial for coordinating movement. This molecular code, based on Hox genes, explains how these neurons differ, even within the same spinal cord column, revealing cellular heterogeneity essential for proprioception.

Keywords:
GdnfHox clusterHox geneHoxc9miR-196microRNAproprioceptionsensory neuronspinal cord patterningspinocerebellar

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Genetics

Background:

  • Coordinated movement relies on proprioception, the sense of body position and force.
  • Proprioceptive signals travel to the cerebellum via spinocerebellar neurons in the spinal cord.
  • Molecular understanding of spinocerebellar neuron heterogeneity is limited.

Purpose of the Study:

  • To explore the molecular heterogeneity of spinocerebellar relay interneurons.
  • To identify molecular markers defining different spinocerebellar neuron populations.
  • To investigate the role of Hox genes in spinocerebellar neuron regionalization.

Main Methods:

  • Utilized fluorescent reporter mice for cell identification.
  • Employed neuronal tracing techniques to map connections.
  • Performed in situ hybridization to analyze gene expression patterns.
  • Investigated the function of specific Hox genes, like Hoxc9.

Main Results:

  • Identified widespread expression of Hox cluster genes in spinocerebellar neurons.
  • Revealed a
  • Hox code
  • correlating with axial level and spinocerebellar column identity.
  • Demonstrated that Hoxc9 is essential for the regionalization of thoracic spinocerebellar column subtypes, including Clarke's column.
  • Uncovered cellular heterogeneity within the thoracic spinocerebellar column based on Hox gene expression signatures.

Conclusions:

  • Hox genes establish a molecular code that defines spinocerebellar neuron identity and regionalization.
  • This Hox code is critical for organizing neuronal subtypes within specific spinal cord levels and columns.
  • The findings reveal intrinsic molecular heterogeneity within spinocerebellar populations, essential for proprioceptive relay and motor control.