title: Ezh2 regulates anteroposterior axis specification and proximodistal axis elongation in the developing limb.
abstract: 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.
authors.affiliation: Developmental and Stem Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Wyngaarden
authors.forename: Paul
authors.initials: P
authors.lastname: Delgado-Olguin
authors.forename: I-hsin
authors.initials: IH
authors.lastname: Su
authors.forename: Benoit G
authors.initials: BG
authors.lastname: Bruneau
authors.forename: Sevan
authors.initials: S
authors.lastname: Hopyan
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation; D000071221:Enhancer of Zeste Homolog 2 Protein; D005121:Extremities / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D018878:Limb Buds / Q000378:metabolism*; D051379:Mice; D063151:Polycomb Repressive Complex 2; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2