Hox Proteins Coordinate Motor Neuron Differentiation and Connectivity Programs through Ret/Gfrα Genes
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....
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-03-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716300602 |
| _version_ | 1818968020770357248 |
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| author | Catarina Catela Maggie M. Shin David H. Lee Jeh-Ping Liu Jeremy S. Dasen |
| author_facet | Catarina Catela Maggie M. Shin David H. Lee Jeh-Ping Liu Jeremy S. Dasen |
| author_sort | Catarina Catela |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T13:58:03Z |
| format | Article |
| id | doaj.art-8435615548f041fe9c730d88f68e0310 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-20T13:58:03Z |
| publishDate | 2016-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-8435615548f041fe9c730d88f68e03102022-12-21T19:38:24ZengElsevierCell Reports2211-12472016-03-011481901191510.1016/j.celrep.2016.01.067Hox Proteins Coordinate Motor Neuron Differentiation and Connectivity Programs through Ret/Gfrα GenesCatarina Catela0Maggie M. Shin1David H. Lee2Jeh-Ping Liu3Jeremy S. Dasen4Neuroscience Institute, Department of Neuroscience and Physiology, NYU School of Medicine, New York, NY 10016, USANeuroscience Institute, Department of Neuroscience and Physiology, NYU School of Medicine, New York, NY 10016, USANeuroscience Institute, Department of Neuroscience and Physiology, NYU School of Medicine, New York, NY 10016, USADepartment of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA 22908, USANeuroscience Institute, Department of Neuroscience and Physiology, NYU School of Medicine, New York, NY 10016, USAThe 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.http://www.sciencedirect.com/science/article/pii/S2211124716300602 |
| spellingShingle | Catarina Catela Maggie M. Shin David H. Lee Jeh-Ping Liu Jeremy S. Dasen Hox Proteins Coordinate Motor Neuron Differentiation and Connectivity Programs through Ret/Gfrα Genes Cell Reports |
| title | Hox Proteins Coordinate Motor Neuron Differentiation and Connectivity Programs through Ret/Gfrα Genes |
| title_full | Hox Proteins Coordinate Motor Neuron Differentiation and Connectivity Programs through Ret/Gfrα Genes |
| title_fullStr | Hox Proteins Coordinate Motor Neuron Differentiation and Connectivity Programs through Ret/Gfrα Genes |
| title_full_unstemmed | Hox Proteins Coordinate Motor Neuron Differentiation and Connectivity Programs through Ret/Gfrα Genes |
| title_short | Hox Proteins Coordinate Motor Neuron Differentiation and Connectivity Programs through Ret/Gfrα Genes |
| title_sort | hox proteins coordinate motor neuron differentiation and connectivity programs through ret gfrα genes |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716300602 |
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