Cited by 73Developmental Biology and Gene RegulationAxon Guidance and Neuronal SignalingNeurogenesis and neuroplasticity mechanisms

Hox proteins coordinate motor neuron differentiation and connectivity programs through Ret/Gfrα genes

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Catela, Catarina, Shin, Maggie M., Lee, David H., Liu, Jeh-Ping, Dasen, Jeremy S.·2016·Cell Reports

Abstract

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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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)
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
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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