title: Hox Proteins Coordinate Motor Neuron Differentiation and Connectivity Programs through Ret/Gfrα Genes.
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.
authors.affiliation: Neuroscience Institute, Department of Neuroscience and Physiology, NYU School of Medicine, New York, NY 10016, USA.
authors.forename: Catarina
authors.initials: C
authors.lastname: Catela
authors.affiliation: Neuroscience Institute, Department of Neuroscience and Physiology, NYU School of Medicine, New York, NY 10016, USA.
authors.forename: Maggie M
authors.initials: MM
authors.lastname: Shin
authors.affiliation: Neuroscience Institute, Department of Neuroscience and Physiology, NYU School of Medicine, New York, NY 10016, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors.forename: Jeh-Ping
authors.initials: JP
authors.lastname: Liu
authors.affiliation: Neuroscience Institute, Department of Neuroscience and Physiology, NYU School of Medicine, New York, NY 10016, USA. Electronic address: jeremy.dasen@nyumc.org.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Dasen
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002642:Chick Embryo; D004622:Embryo, Mammalian; D005552:Forelimb; D018507:Gene Expression Regulation, Developmental; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism* / Q000648:ultrastructure; D009154:Mutation; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics* / Q000378:metabolism; D013116:Spinal Cord / Q000254:growth & development / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission; D014157:Transcription Factors; D014158:Transcription, Genetic
chemical_list: C494988:Gfra1 protein, mouse; C494994:Gfra3 protein, mouse; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D018398:Homeodomain Proteins; C059637:Hoxa5 protein, mouse; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D014157:Transcription Factors; D051096:Proto-Oncogene Proteins c-ret; C494999:Ret protein, mouse