title: Podoplanin deficient mice show a RhoA-related hypoplasia of the sinus venosus myocardium including the sinoatrial node.
abstract: We investigated the role of podoplanin in development of the sinus venosus myocardium comprising the sinoatrial node, dorsal atrial wall, and primary atrial septum as well as the myocardium of the cardinal and pulmonary veins. We analyzed podoplanin wild-type and knockout mouse embryos between embryonic day 9.5-15.5 using immunohistochemical marker podoplanin; sinoatrial-node marker HCN4; myocardial markers MLC-2a, Nkx2.5, as well as Cx43; coelomic marker WT-1; and epithelial-to-mesenchymal transformation markers E-cadherin and RhoA. Three-dimensional reconstructions were made and myocardial morphometry was performed. Podoplanin mutants showed hypoplasia of the sinoatrial node, primary atrial septum, and dorsal atrial wall. Myocardium lining the wall of the cardinal and pulmonary veins was thin and perforated. Impaired myocardial formation is correlated with abnormal epithelial-to-mesenchymal transformation of the coelomic epithelium due to up-regulated E-cadherin and down-regulated RhoA, which are controlled by podoplanin. Our results demonstrate an important role for podoplanin in development of sinus venosus myocardium.
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, The Netherlands.
authors.forename: Edris A F
authors.initials: EA
authors.lastname: Mahtab
authors.forename: Rebecca
authors.initials: R
authors.lastname: Vicente-Steijn
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Hahurij
authors.forename: Monique R M
authors.initials: MR
authors.lastname: Jongbloed
authors.forename: Lambertus J
authors.initials: LJ
authors.lastname: Wisse
authors.forename: Marco C
authors.initials: MC
authors.lastname: DeRuiter
authors.forename: Pavel
authors.initials: P
authors.lastname: Uhrin
authors.forename: Jan
authors.initials: J
authors.lastname: Zaujec
authors.forename: Bernd R
authors.initials: BR
authors.lastname: Binder
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Schalij
authors.forename: Robert E
authors.initials: RE
authors.lastname: Poelmann
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Gittenberger-de Groot
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D004848:Epithelium / Q000502:physiology; D005260:Female; D006325:Heart Atria / Q000002:abnormalities / Q000033:anatomy & histology / Q000196:embryology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D012849:Sinoatrial Node / Q000002:abnormalities / Q000196:embryology; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D000098853:Podoplanin
chemical_list: D015415:Biomarkers; D008562:Membrane Glycoproteins; D020742:rhoA GTP-Binding Protein; C490441:Pdpn protein, mouse; D000098853:Podoplanin