Muscle-type Identity of Proprioceptors Specified by Spatially Restricted Signals from Limb Mesenchyme

Cell. 2016 Jan 28;164(3):512-25. doi: 10.1016/j.cell.2015.12.049.

Abstract

The selectivity with which proprioceptive sensory neurons innervate their central and peripheral targets implies that they exhibit distinctions in muscle-type identity. The molecular correlates of proprioceptor identity and its origins remain largely unknown, however. In screens to define muscle-type proprioceptor character, we find all-or-none differences in gene expression for proprioceptors that control antagonistic muscles at a single hindlimb joint. Analysis of three of these genes, cadherin13 (cdh13), semaphorin5a (sema5a), and cartilage-acidic protein-1 (crtac1), reveals expression in proprioceptor subsets that supply muscle groups located at restricted dorsoventral and proximodistal domains of the limb. Genetically altering the dorsoventral character of the limb mesenchyme elicits a change in the profile of proprioceptor cdh13, sema5a, and crtac1 expression. These findings indicate that proprioceptors acquire aspects of their muscle-type identity in response to mesenchymal signals expressed in restricted proximodistal and dorsoventral domains of the developing limb.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / genetics
  • Calcium-Binding Proteins / genetics
  • Embryo, Mammalian / metabolism
  • Extremities / embryology*
  • Extremities / physiology
  • Mesoderm / metabolism*
  • Mice
  • Muscle, Skeletal / innervation
  • Neurons / metabolism
  • Proprioception*
  • Semaphorins / genetics
  • Signal Transduction
  • Transcriptome

Substances

  • Cadherins
  • Calcium-Binding Proteins
  • Crtac1 protein, mouse
  • H-cadherin
  • Sema5A protein, mouse
  • Semaphorins