Origin and segmental diversity of spinal inhibitory interneurons
Open accessAbstract
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.
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Combinatorial expression of 19 TFs has been proposed to generate multiple subpopulations of V1 interneurons.
“Moreover, the combinatorial expression of 19 TFs have been proposed to generate multiple subpopulations of V1 interneurons (Bikoff et al., 2016; Gabitto et al., 2016; Sweeney et al., 2018).”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Sweeney et al., 2018
Neuronal subtypes vary along the rostral caudal axis of the neural tube.
“In addition, neuronal subtypes vary along the rostral caudal axis of the neural tube (Hayashi et al., 2018; Philippidou and Dasen, 2013; Sweeney et al., 2018).”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Sweeney et al., 2018
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- Authors
- Sweeney, L. B., Bikoff, J. B., Gabitto, M. I., Brenner-Morton, S., Baek, M., Yang, J. H., Tabak, E. G., Dasen, J. S., Kintner, C. R., & Jessell, T. M.
- Affiliations
- Salk Institute for Biological Studies (US)
- Howard Hughes Medical Institute (US)
- Simons Foundation (US)
- Courant Institute of Mathematical Sciences (US)
- NYU Langone Health (US)
- Corresponding author
- Sweeney, Lora B.
- Gabitto, Mariano I.
- Jessell, Thomas M.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 97
- Issue
- 2
- Pages
- 341-355.e3
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC5880537
- OpenAlex
- W2781607143
- Cited by
- 116
- References
- 57
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 24 · 2023: 12 · 2022: 12 · 2021: 15 · 2020: 11 · 2019: 15 · 2018: 11
- FWCI
- 4.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH-NCI CCSG (P30 014195)
- NINDS Neuroscience Core (NS072031)
- Waitt Foundation
- Damon Runyon Cancer Foundation
- Project ALS (R01 NS062822, R01 NS097550, R01 NS033245)
- Brain Research Foundation
- Office of Naval Research (N000141310117)
- National Science Foundation (1211298, R01 GM076507)
- Harold and Leila Y. Mathers Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
- Keywords
- HOXC9, transcription factors, motor pools, rostrocaudal axis, interneuron diversity, spinal cord development
- MeSH terms
- Animals, Bayes Theorem, Forelimb, Genes, Homeobox, Hindlimb, Interneurons, Lumbosacral Region, Motor Neurons, Nerve Tissue Proteins, Spinal Cord, Thorax, Transcription Factors, Mice, Knockout, Homeodomain Proteins, Gene Expression Profiling, Mice
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