| Polycomb repressive complex 1 activities determine the columnar organization of motor neurons. | |
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MedLine Citation:
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PMID: 23028147 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Polycomb repressive complexes (PRCs) establish and maintain gene repression through chromatin modifications, but their specific roles in cell fate determination events are poorly understood. Here we show an essential role for the PRC1 component Bmi1 in motor neuron (MN) subtype differentiation through dose-dependent effects on Hox gene expression. While Bmi1 is dispensable for generating MNs as a class, it has an essential role in specifying and determining the position of Hox-dependent MN columnar and pool subtypes. These actions are mediated through limiting anterior Hox expression boundaries, functions deployed in post-mitotic MNs, temporally downstream from morphogen gradients. Within the HoxC gene cluster, we found a progressive depletion of PRC-associated marks from rostral to caudal levels of the spinal cord, corresponding to major demarcations of MN subtypes. Selective ablation of Bmi1 elicits a derepression of more posterior Hox genes, leading to a switch in MN fates. Unexpectedly, Hox patterns and MN fates appear to be sensitive to absolute PRC1 activity levels; while reducing Bmi1 switches forelimb lateral motor column (LMC) MNs to a thoracic preganglionic (PGC) identity, elevating Bmi1 expression at thoracic levels converts PGC to LMC MNs. These results suggest that graded PRC1 activities are essential in determining MN topographic organization. |
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Authors:
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Molly G Golden; Jeremy S Dasen |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Genes & development Volume: 26 ISSN: 1549-5477 ISO Abbreviation: Genes Dev. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-02 Completed Date: 2012-12-05 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 8711660 Medline TA: Genes Dev Country: United States |
Other Details:
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Languages: eng Pagination: 2236-50 Citation Subset: IM |
Affiliation:
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Department of Physiology and Neuroscience, Smilow Neuroscience Program, Howard Hughes Medical Institute, New York University School of Medicine, New York, New York 10016, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Gene Expression Profiling Gene Expression Regulation, Developmental* Genes, Homeobox / genetics Mice Motor Neurons / cytology*, metabolism Polycomb Repressive Complex 1 / genetics*, metabolism* Proto-Oncogene Proteins / genetics, metabolism* Signal Transduction Spinal Cord / metabolism Stem Cells / cytology, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 NS062822/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Bmi1 protein, mouse; 0/Proto-Oncogene Proteins; EC 6.3.2.19/Polycomb Repressive Complex 1 |
| Comments/Corrections | |
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