title: The ciliary protein Ftm is required for ventricular wall and septal development.
abstract: Ventricular septal defects (VSDs) are the most common congenital heart defects in humans. Despite several studies of the molecular mechanisms involved in ventricular septum (VS) development, very little is known about VS-forming signaling. We observed perimembranous and muscular VSDs in Fantom (Ftm)-negative mice. Since Ftm is a ciliary protein, we investigated presence and function of cilia in murine hearts. Primary cilia could be detected at distinct positions in atria and ventricles at embryonic days (E) 10.5-12.5. The loss of Ftm leads to shortened cilia and a reduced proliferation in distinct atrial and ventricular ciliary regions at E11.5. Consequently, wall thickness is diminished in these areas. We suggest that ventricular proliferation is regulated by cilia-mediated Sonic hedgehog (Shh) and platelet-derived growth factor receptor α (Pdgfrα) signaling. Accordingly, we propose that primary cilia govern the cardiac proliferation which is essential for proper atrial and ventricular wall development and hence for the fully outgrowth of the VS. Thus, our study suggests ciliopathy as a cause of VSDs.
authors.affiliation: Institute for Animal Developmental and Molecular Biology, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Gerhardt
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Lier
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kuschel
authors.forename: Ulrich
authors.initials: U
authors.lastname: Rüther
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002923:Cilia / Q000378:metabolism*; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D006346:Heart Septum / Q000196:embryology*; D006352:Heart Ventricles / Q000196:embryology*; D051379:Mice; D008809:Mice, Inbred C3H; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; C523257:Ftm protein, mouse