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Publication : Ezh2 regulates anteroposterior axis specification and proximodistal axis elongation in the developing limb.

First Author  Wyngaarden LA Year  2011
Journal  Development Volume  138
Issue  17 Pages  3759-67
PubMed ID  21795281 Mgi Jnum  J:175770
Mgi Id  MGI:5287304 Doi  10.1242/dev.063180
Citation  Wyngaarden LA, et al. (2011) Ezh2 regulates anteroposterior axis specification and proximodistal axis elongation in the developing limb. Development 138(17):3759-67
abstractText  Specification and determination (commitment) of positional identities precedes overt pattern formation during development. In the limb bud, it is clear that the anteroposterior axis is specified at a very early stage and is prepatterned by the mutually antagonistic interaction between Gli3 and Hand2. There is also evidence that the proximodistal axis is specified early and determined progressively. Little is known about upstream regulators of these processes or how epigenetic modifiers influence axis formation. Using conditional mutagenesis at different time points, we show that the histone methyltransferase Ezh2 is an upstream regulator of anteroposterior prepattern at an early stage. Mutants exhibit posteriorised limb bud identity. During later limb bud stages, Ezh2 is essential for cell survival and proximodistal segment elongation. Ezh2 maintains the late phase of Hox gene expression and cell transposition experiments suggest that it regulates the plasticity with which cells respond to instructive positional cues.
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