Document Detail


Polycomb repressive complex 1 activities determine the columnar organization of motor neurons.
MedLine Citation:
PMID:  23028147     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Molly G Golden; Jeremy S Dasen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Genes & development     Volume:  26     ISSN:  1549-5477     ISO Abbreviation:  Genes Dev.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-02     Completed Date:  2012-12-05     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2236-50     Citation Subset:  IM    
Affiliation:
Department of Physiology and Neuroscience, Smilow Neuroscience Program, Howard Hughes Medical Institute, New York University School of Medicine, New York, New York 10016, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
R01 NS062822/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Bmi1 protein, mouse; 0/Proto-Oncogene Proteins; EC 6.3.2.19/Polycomb Repressive Complex 1
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