Parallel Pbx-dependent pathways govern the coalescence and fate of motor columns
Open accessAbstract
The clustering of neurons sharing similar functional properties and connectivity is a common organizational feature of vertebrate nervous systems. Within motor networks, spinal motor neurons (MNs) segregate into longitudinally arrayed subtypes, establishing a central somatotopic map of peripheral target innervation. MN organization and connectivity relies on Hox transcription factors expressed along the rostrocaudal axis; however, the developmental mechanisms governing the orderly arrangement of MNs are largely unknown. We show that Pbx genes, which encode Hox cofactors, are essential for the segregation and clustering of neurons within motor columns. In the absence of Pbx1 and Pbx3 function, Hox-dependent programs are lost and the remaining MN subtypes are unclustered and disordered. Identification of Pbx gene targets revealed an unexpected and apparently Hox-independent role in defining molecular features of dorsally projecting medial motor column (MMC) neurons. These results indicate Pbx genes act in parallel genetic pathways to orchestrate neuronal subtype differentiation, connectivity, and organization.
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The analysis correctly predicted that Pcdh7, Megf11 and Ret are expressed in MNs.
“Consistent with previous work, the analysis correctly predicted that Pcdh7, Megf11 and Ret are expressed in MNs”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Hanley et al., 2016
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- Rhee JW Arata A Selleri L Jacobs Y Arata S Onimaru H Cleary ML 2004b Pbx3 Deficiency Results in Central Hypoventilation The American Journal of Pathology 165 1343 1350 15466398 PMC1618620
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Delile, J., Rayon, T., Melchionda, M., Edwards, A., Briscoe, J., & Sagner, A. (2019) · Development · doi:10.1242/dev.173807 · Cited by 356 · see citing works
- Authors
- Hanley, O., Zewdu, R., Cohen, L. J., Jung, H., Lacombe, J., Philippidou, P., Lee, D. H., Selleri, L., & Dasen, J. S.
- Affiliations
- NYU Langone Health (US)
- Weill Cornell Medicine (US)
- Corresponding author
- Dasen, Jeremy S.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 91
- Issue
- 5
- Pages
- 1005-1020
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC5017921
- OpenAlex
- W2517933970
- Cited by
- 49
- References
- 54
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 11 · 2023: 5 · 2022: 6 · 2021: 3 · 2020: 1 · 2019: 7 · 2018: 4 · 2017: 3 · 2016: 1
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- NYU Langone Medical Center
- National Institutes of Health (UL1TR000038, UL1TR001445)
- National Cancer Institute (P30CA016087)
- National Institute of Neurological Disorders and Stroke (R01NS097550, R00NS085037, R01NS062822)
- National Institute of Dental and Craniofacial Research (R01DE024745)
- National Center for Advancing Translational Sciences
- 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 › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Keywords
- PBX1, PBX3, spinal motoneurons, motor neuron subtypes, neuronal clustering, somatotopic map, rostrocaudal axis
- MeSH terms
- Pre-B-Cell Leukemia Transcription Factor 1, Aldehyde Oxidoreductases, Animals, Cell Differentiation, Chick Embryo, Gene Expression Regulation, Motor Neurons, Mutation, Proto-Oncogene Proteins, Repressor Proteins, Spinal Cord, Transcription Factors, Homeodomain Proteins, Mice, Forkhead Transcription Factors
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