Hox proteins coordinate motor neuron differentiation and connectivity programs through Ret/Gfrα genes
Open accessAbstract
The accuracy of neural circuit assembly relies on the precise spatial and temporal control of synaptic specificity determinants during development. Hox transcription factors govern key aspects of motor neuron (MN) differentiation; however, the terminal effectors of their actions are largely unknown. We show that Hox/Hox cofactor interactions coordinate MN subtype diversification and connectivity through Ret/Gfrα receptor genes. Hox and Meis proteins determine the levels of Ret in MNs and define the intrasegmental profiles of Gfrα1 and Gfrα3 expression. Loss of Ret or Gfrα3 leads to MN specification and innervation defects similar to those observed in Hox mutants, while expression of Ret and Gfrα1 can bypass the requirement for Hox genes during MN pool differentiation. These studies indicate that Hox proteins contribute to neuronal fate and muscle connectivity through controlling the levels and pattern of cell surface receptor expression, consequently gating the ability of MNs to respond to limb-derived instructive cues.
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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 Catela et al., 2016
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- Authors
- Catela, C., Shin, M. M., Lee, D. H., Liu, J.-P., & Dasen, J. S.
- Affiliations
- NYU Langone Health (US)
- University of Virginia (US)
- Corresponding author
- Dasen, Jeremy S.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 14
- Issue
- 8
- Pages
- 1901-1915
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC4775310
- OpenAlex
- W2287678585
- Cited by
- 73
- References
- 49
- Citations by year
- 2025: 4 · 2024: 7 · 2023: 7 · 2022: 13 · 2021: 8 · 2020: 8 · 2019: 7 · 2018: 7 · 2017: 8 · 2016: 4
- FWCI
- 4.50
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS045933, R01NS062822, T32NS086750)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- Hox transcription factors, motor neuron differentiation, RET receptor, GFRα1, GFRα3, muscle innervation, synaptic specificity, neural circuit assembly, neuronal fate specification
- MeSH terms
- Myeloid Ecotropic Viral Integration Site 1 Protein, Animals, Cell Differentiation, Chick Embryo, Embryo, Mammalian, Forelimb, Motor Neurons, Mutation, Neoplasm Proteins, Synaptic Transmission, Phosphoproteins, Spinal Cord, Synapses, Transcription Factors, Transcription, Genetic, Homeodomain Proteins, Muscle, Skeletal, Gene Expression Regulation, Developmental, Protein Isoforms, Proto-Oncogene Proteins c-ret, Glial Cell Line-Derived Neurotrophic Factor Receptors, Mice, Neurogenesis
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