Origin and Segmental Diversity of Spinal Inhibitory Interneurons

Neuron. 2018 Jan 17;97(2):341-355.e3. doi: 10.1016/j.neuron.2017.12.029. Epub 2018 Jan 4.

Abstract

Motor output varies along the rostro-caudal axis of the tetrapod spinal cord. At limb levels, ∼60 motor pools control the alternation of flexor and extensor muscles about each joint, whereas at thoracic levels as few as 10 motor pools supply muscle groups that support posture, inspiration, and expiration. Whether such differences in motor neuron identity and muscle number are associated with segmental distinctions in interneuron diversity has not been resolved. We show that select combinations of nineteen transcription factors that specify lumbar V1 inhibitory interneurons generate subpopulations enriched at limb and thoracic levels. Specification of limb and thoracic V1 interneurons involves the Hox gene Hoxc9 independently of motor neurons. Thus, early Hox patterning of the spinal cord determines the identity of V1 interneurons and motor neurons. These studies reveal a developmental program of V1 interneuron diversity, providing insight into the organization of inhibitory interneurons associated with differential motor output.

Keywords: Hox proteins; cell identity; development; inhibitory interneurons; motor circuit; spinal cord patterning; transcription factor.

Publication types

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

MeSH terms

  • Animals
  • Bayes Theorem
  • Forelimb / embryology
  • Forelimb / innervation
  • Gene Expression Profiling
  • Genes, Homeobox*
  • Hindlimb / embryology
  • Hindlimb / innervation
  • Homeodomain Proteins / physiology
  • Interneurons / physiology
  • Lumbosacral Region
  • Mice
  • Mice, Knockout
  • Motor Neurons / physiology
  • Nerve Tissue Proteins / physiology
  • Spinal Cord / cytology*
  • Spinal Cord / embryology
  • Thorax
  • Transcription Factors / physiology

Substances

  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Transcription Factors