Molecular Logic of Spinocerebellar Tract Neuron Diversity and Connectivity
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Abstract
Coordinated motor behaviors depend on feedback communication between peripheral sensory systems and central circuits in the brain and spinal cord. Relay of muscle- and tendon-derived sensory information to the CNS is facilitated by functionally and anatomically diverse groups of spinocerebellar tract neurons (SCTNs), but the molecular logic by which SCTN diversity and connectivity is achieved is poorly understood. We used single-cell RNA sequencing and genetic manipulations to define the mechanisms governing the molecular profile and organization of SCTN subtypes. We found that SCTNs relaying proprioceptive sensory information from limb and axial muscles are generated through segmentally restricted actions of specific Hox genes. Loss of Hox function disrupts SCTN-subtype-specific transcriptional programs, leading to defects in the connections between proprioceptive sensory neurons, SCTNs, and the cerebellum. These results indicate that Hox-dependent genetic programs play essential roles in the assembly of neural circuits necessary for communication between the brain and spinal cord.
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The merged dataset contains over one hundred thousand cells and nuclei from the first six published studies of the postnatal mouse spinal cord.
“We first created a merged dataset with over one hundred thousand cells and nuclei from the first six published studies of the postnatal mouse spinal cord1–6.”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [6]
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A harmonized atlas of mouse spinal cord cell types and their spatial organization
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- Authors
- Baek, M., Menon, V., Jessell, T. M., Hantman, A. W., & Dasen, J. S.
- Affiliations
- Howard Hughes Medical Institute (US)
- Columbia University Irving Medical Center (US)
- NYU Langone Health (US)
- Corresponding author
- Hantman, Adam W.
- Dasen, Jeremy S.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 27
- Issue
- 9
- Pages
- 2620-2635.e4
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC6555431
- OpenAlex
- W2951960082
- Cited by
- 56
- References
- 55
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 7 · 2023: 10 · 2022: 10 · 2021: 9 · 2020: 7 · 2019: 1
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- Hox genes, proprioception, sensory neuron subtypes, cerebellum, spinal cord, neural circuit assembly, transcriptional programs, single-cell RNA sequencing
- MeSH terms
- Animals, Female, Gene Expression Regulation, Male, Motor Neurons, Nerve Net, Sensory Receptor Cells, Mice, Knockout, Homeodomain Proteins, Spinocerebellar Tracts, Gene Expression Profiling
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