title: Pitx2c modulates Pax3+/Pax7+ cell populations and regulates Pax3 expression by repressing miR27 expression during myogenesis.
abstract: Pitx2 is a paired-related homeobox gene that is expressed in muscle progenitors during myogenesis. We have previously demonstrated that overexpression of Pitx2c isoform in myoblasts maintained these cells with a high proliferative capacity and completely blocked terminal differentiation by inducing high Pax3 expression levels (Martinez et al., 2006). We now report that Pitx2c-mediated proliferation vs. differentiation effect is maintained during in vivo myogenesis. In vivo Pitx2c loss of function leads to a decrease in Pax3+/Pax7- cell population in the embryo accompanied by an increase of Pax3+/Pax7+ cells. Pitx2c transient-transfection experiments further supported the notion that Pitx2c can modulate Pax3/Pax7 expression. Pitx2c but not Pitx3 controls Pax3/Pax7 expression, although redundant roles are elicited at the terminal myoblast differentiation. Contrary to Pitx2c, Pitx3 does not regulate cell proliferation or Pax3 expression, demonstrating the specificity of Pitx2c mediating these actions in myoblasts. Furthermore we demonstrated that Pitx2c modulates Pax3 by repressing miR27 expression and that Pax3-miR-27 modulation mediated by Pitx2c is independent of Pitx2c effects on cell proliferation. Therefore, this study sheds light on previously unknown function of Pitx2c balancing the different myogenic progenitor populations during myogenesis.
authors.affiliation: Department of Experimental Biology, Faculty of Experimental Sciences, University of Jaen, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Lozano-Velasco
authors.forename: Alejandra
authors.initials: A
authors.lastname: Contreras
authors.forename: Colin
authors.initials: C
authors.lastname: Crist
authors.forename: Francisco
authors.initials: F
authors.lastname: Hernández-Torres
authors.forename: Diego
authors.initials: D
authors.lastname: Franco
authors.forename: Amelia E
authors.initials: AE
authors.lastname: Aránega
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D024510:Muscle Development / Q000235:genetics*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D000072041:PAX3 Transcription Factor; D051763:PAX7 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D051761:Paired Box Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D000097577:Homeobox Protein PITX2
chemical_list: D018398:Homeodomain Proteins; D035683:MicroRNAs; D000072041:PAX3 Transcription Factor; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C497322:Pax7 protein, mouse; C068686:Pax3 protein, mouse