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

Origin and Segmental Diversity of Spinal Inhibitory Interneurons.

Author information

1
Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: lsweeney@salk.edu.
2
Howard Hughes Medical Institute, Zuckerman Institute, Departments of Neuroscience, and Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
3
Center for Computational Biology, Flatiron Institute, Simons Foundation, New York, NY 10010, USA. Electronic address: mgabitto@simonsfoundation.org.
4
Neuroscience Institute, Department of Neuroscience and Physiology, NYU School of Medicine, New York, NY 10016, USA.
5
Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
6
Courant Institute of Mathematical Sciences, New York University, New York, NY 10012, USA.
7
Howard Hughes Medical Institute, Zuckerman Institute, Departments of Neuroscience, and Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. Electronic address: tmj1@cumc.columbia.edu.

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

PMID:
29307712
PMCID:
PMC5880537
[Available on 2019-01-17]
DOI:
10.1016/j.neuron.2017.12.029

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