Global control of motor neuron topography mediated by the repressive actions of a single hox gene Journal Article
| Authors: | Jung, H.; Lacombe, J.; Mazzoni, E. O.; Liem, K. F. Jr; Grinstein, J.; Mahony, S.; Mukhopadhyay, D.; Gifford, D. K.; Young, R. A.; Anderson, K. V.; Wichterle, H.; Dasen, J. S. |
| Article Title: | Global control of motor neuron topography mediated by the repressive actions of a single hox gene |
| Abstract: | In the developing spinal cord, regional and combinatorial activities of Hox transcription factors are critical in controlling motor neuron fates along the rostrocaudal axis, exemplified by the precise pattern of limb innervation by more than fifty Hox-dependent motor pools. The mechanisms by which motor neuron diversity is constrained to limb levels are, however, not well understood. We show that a single Hox gene, Hoxc9, has an essential role in organizing the motor system through global repressive activities. Hoxc9 is required for the generation of thoracic motor columns, and in its absence, neurons acquire the fates of limb-innervating populations. Unexpectedly, multiple Hox genes are derepressed in Hoxc9 mutants, leading to motor pool disorganization and alterations in the connections by thoracic and forelimb-level subtypes. Genome-wide analysis of Hoxc9 binding suggests that this mode of repression is mediated by direct interactions with Hox regulatory elements, independent of chromatin marks typically associated with repressed Hox genes. © 2010 Elsevier Inc. |
| Keywords: | controlled study; protein expression; unclassified drug; gene cluster; gene mutation; mutation; nonhuman; genetic analysis; forkhead transcription factors; mouse; phenotype; animals; mice; animal tissue; gene expression profiling; smad1 protein; embryo; protein protein interaction; protein binding; rna, small interfering; gene function; homeodomain proteins; mice, transgenic; gene expression regulation, developmental; chromatin immunoprecipitation; spinal cord; motor neurons; extremities; green fluorescent proteins; electroporation; sacrococcygeal region; dna mutational analysis; animals, newborn; repressor proteins; axons; nitric oxide synthase type i; hox protein; motoneuron; chick embryo; transcription factor hoxa9; transcription factor hoxc9; biodiversity; genetic transformation; aldehyde oxidoreductases |
| Journal Title: | Neuron |
| Volume: | 67 |
| Issue: | 5 |
| ISSN: | 0896-6273 |
| Publisher: | Cell Press |
| Date Published: | 2010-09-09 |
| Start Page: | 781 |
| End Page: | 796 |
| Language: | English |
| DOI: | 10.1016/j.neuron.2010.08.008 |
| PUBMED: | 20826310 |
| PROVIDER: | scopus |
| PMCID: | PMC2955411 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: NERNE" - "Source: Scopus" |
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