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Publication : Polycomb repressive complex 1 activities determine the columnar organization of motor neurons.

First Author  Golden MG Year  2012
Journal  Genes Dev Volume  26
Issue  19 Pages  2236-50
PubMed ID  23028147 Mgi Jnum  J:188258
Mgi Id  MGI:5440100 Doi  10.1101/gad.199133.112
Citation  Golden MG, et al. (2012) Polycomb repressive complex 1 activities determine the columnar organization of motor neurons. Genes Dev 26(19):2236-50
abstractText  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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