title: Cardiac differentiation in Xenopus is initiated by mespa.
abstract: OBJECTIVE
  Future cardiac repair strategies will require a profound understanding of the principles underlying cardiovascular differentiation. Owing to its extracorporal and rapid development, Xenopus laevis provides an ideal experimental system to address these issues in vivo. Whereas mammalian MesP1 is currently regarded as the earliest marker for the cardiovascular system, several MesP1-related factors from Xenopus-mespa, mespb, and mespo-have been assigned only to somitogenesis so far. We, therefore, analysed these genes comparatively for potential contributions to cardiogenesis.
  
  
  RESULTS
  RNA in situ hybridizations revealed a novel anterior expression domain exclusively occupied by mespa during gastrulation, which precedes the prospective heart field. Correspondingly, when overexpressed mespa most strongly induced cardiac markers in vivo as well as ex vivo. Transference to murine embryonic stem (ES) cells and subsequent FACS analyses for Flk-1 and Troponin I confirmed the high potential of mespa as a cardiac inducer. In vivo, Morpholino-based knockdown of mespa protein led to a dramatic loss of pro-cardiac and sarcomeric markers, which could be rescued either by mespa itself or human MesP1, but neither by mespb nor mespo. Epistatic analysis positioned mespa upstream of mespo and mespb, and revealed positive autoregulation for mespa at the time of its induction.
  
  
  CONCLUSIONS
  Our findings contribute to the understanding of conserved events initiating vertebrate cardiogenesis. We identify mespa as functional amphibian homologue of mammalian MesP1. These results will enable the dissection of cardiac specification from the very beginning in the highly versatile Xenopus system.
authors.affiliation: Department of Molecular Biology,  Adolf-Butenandt-Institute, University of Munich LMU, Schillerstraβe 44, 80336 München,  Germany.
authors.forename: Maximilian C M
authors.initials: MC
authors.lastname: Kriegmair
authors.forename: Stephanie
authors.initials: S
authors.lastname: Frenz
authors.forename: Marina
authors.initials: M
authors.lastname: Dusl
authors.forename: Wolfgang-M
authors.initials: WM
authors.lastname: Franz
authors.forename: Robert
authors.initials: R
authors.lastname: David
authors.forename: Ralph A W
authors.initials: RA
authors.lastname: Rupp
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006321:Heart / Q000196:embryology* / Q000502:physiology; D051379:Mice; D023421:Models, Animal; D060172:Morpholinos / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology; D029867:Xenopus Proteins / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology* / Q000502:physiology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D060172:Morpholinos; D029867:Xenopus Proteins; C583266:Mespa protein, Xenopus; C530218:Mespb protein, Xenopus; C534575:Msgn1 protein, Xenopus