Origin and Segmental Diversity of Spinal Inhibitory Interneurons

Lora B. Sweeney, Jay B. Bikoff, Mariano I. Gabitto, Susan Brenner-Morton, Myungin Baek, Jerry H. Yang, Esteban Tabak, Jeremy S. Dasen, Christopher R. Kintner, Thomas M. Jessell

Research output: Contribution to journalArticle

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. Sweeney et al. show that the diversity of spinal inhibitory interneurons, defined by combinatorial transcription factor expression, differs along the body axis in correspondence with limb and thoracic motor output. Hox genes, not motor neurons, specify segmental differences in inhibitory interneuron identity.

Original languageEnglish (US)
JournalNeuron
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Interneurons
Motor Neurons
Thorax
Extremities
Homeobox Genes
Muscles
Spinal Cord
Transcription Factors
Posture
Joints

Keywords

  • Cell identity
  • Development
  • Hox proteins
  • Inhibitory interneurons
  • Motor circuit
  • Spinal cord patterning
  • Transcription factor

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Sweeney, L. B., Bikoff, J. B., Gabitto, M. I., Brenner-Morton, S., Baek, M., Yang, J. H., ... Jessell, T. M. (Accepted/In press). Origin and Segmental Diversity of Spinal Inhibitory Interneurons. Neuron. https://doi.org/10.1016/j.neuron.2017.12.029

Origin and Segmental Diversity of Spinal Inhibitory Interneurons. / Sweeney, Lora B.; Bikoff, Jay B.; Gabitto, Mariano I.; Brenner-Morton, Susan; Baek, Myungin; Yang, Jerry H.; Tabak, Esteban; Dasen, Jeremy S.; Kintner, Christopher R.; Jessell, Thomas M.

In: Neuron, 01.01.2018.

Research output: Contribution to journalArticle

Sweeney, LB, Bikoff, JB, Gabitto, MI, Brenner-Morton, S, Baek, M, Yang, JH, Tabak, E, Dasen, JS, Kintner, CR & Jessell, TM 2018, 'Origin and Segmental Diversity of Spinal Inhibitory Interneurons', Neuron. https://doi.org/10.1016/j.neuron.2017.12.029
Sweeney LB, Bikoff JB, Gabitto MI, Brenner-Morton S, Baek M, Yang JH et al. Origin and Segmental Diversity of Spinal Inhibitory Interneurons. Neuron. 2018 Jan 1. https://doi.org/10.1016/j.neuron.2017.12.029
Sweeney, Lora B. ; Bikoff, Jay B. ; Gabitto, Mariano I. ; Brenner-Morton, Susan ; Baek, Myungin ; Yang, Jerry H. ; Tabak, Esteban ; Dasen, Jeremy S. ; Kintner, Christopher R. ; Jessell, Thomas M. / Origin and Segmental Diversity of Spinal Inhibitory Interneurons. In: Neuron. 2018.
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