title: Regional differences in WT-1 and Tcf21 expression during ventricular development: implications for myocardial compaction.
abstract: BACKGROUND
  Morphological and functional differences of the right and left ventricle are apparent in the adult human heart. A differential contribution of cardiac fibroblasts and smooth muscle cells (populations of epicardium-derived cells) to each ventricle may account for part of the morphological-functional disparity. Here we studied the relation between epicardial derivatives and the development of compact ventricular myocardium.
  
  
  RESULTS
  Wildtype and Wt1CreERT2/+ reporter mice were used to study WT-1 expressing cells, and Tcf21lacZ/+ reporter mice and PDGFRα-/-;Tcf21LacZ/+ mice to study the formation of the cardiac fibroblast population. After covering the heart, intramyocardial WT-1+ cells were first observed at the inner curvature, the right ventricular postero-lateral wall and left ventricular apical wall. Later, WT-1+ cells were present in the walls of both ventricles, but significantly more pronounced in the left ventricle. Tcf21-LacZ + cells followed the same distribution pattern as WT-1+ cells but at later stages, indicating a timing difference between these cell populations. Within the right ventricle, WT-1+ and Tcf21-lacZ+ cell distribution was more pronounced in the posterior inlet part. A gradual increase in myocardial wall thickness was observed early in the left ventricle and at later stages in the right ventricle. PDGFRα-/-;Tcf21LacZ/+ mice showed deficient epicardium, diminished number of Tcf21-LacZ + cells and reduced ventricular compaction.
  
  
  CONCLUSIONS
  During normal heart development, spatio-temporal differences in contribution of WT-1 and Tcf21-LacZ + cells to right versus left ventricular myocardium occur parallel to myocardial thickening. These findings may relate to lateralized differences in ventricular (patho)morphology in humans.
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Vicente-Steijn
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Roderick W C
authors.initials: RW
authors.lastname: Scherptong
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Boudewijn P T
authors.initials: BP
authors.lastname: Kruithof
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Sjoerd N
authors.initials: SN
authors.lastname: Duim
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marie Jose T H
authors.initials: MJ
authors.lastname: Goumans
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Lambertus J
authors.initials: LJ
authors.lastname: Wisse
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; Harvard Stem Cell Institute, Harvard University, Cambridge, and Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Harvard Stem Cell Institute, Harvard University, Cambridge, and Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, United States of America.
authors.forename: William T
authors.initials: WT
authors.lastname: Pu
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Poelmann
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Schalij
authors.affiliation: Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, United States of America.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Tallquist
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Gittenberger-de Groot
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Monique R M
authors.initials: MR
authors.lastname: Jongbloed
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006352:Heart Ventricles / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D025721:WT1 Proteins
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D012097:Repressor Proteins; D025721:WT1 Proteins; C112923:Tcf21 protein, mouse; C000602896:WT1 protein, mouse