The Ciliary Protein Ftm is Required for Ventricular Wall and Septal Development

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Mar 8

PMID 23469020

Citations 23

Authors

Christoph Gerhardt

Johanna M Lier

Stefanie Kuschel

Ulrich Ruther

Affiliations

Soon will be listed here.

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.

Citing Articles

Functions of cilia in cardiac development and disease.

Shaikh Qureshi W, Hentges K Ann Hum Genet. 2023; 88(1):4-26.

PMID: 37872827 PMC: 10952336. DOI: 10.1111/ahg.12534.

Emerging principles of primary cilia dynamics in controlling tissue organization and function.

Gopalakrishnan J, Feistel K, Friedrich B, Grapin-Botton A, Jurisch-Yaksi N, Mass E EMBO J. 2023; 42(21):e113891.

PMID: 37743763 PMC: 10620770. DOI: 10.15252/embj.2023113891.

Life-Saver or Undertaker: The Relationship between Primary Cilia and Cell Death in Vertebrate Embryonic Development.

Pfirrmann T, Gerhardt C J Dev Biol. 2022; 10(4).

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Clustering of Genetic Anomalies of Cilia Outer Dynein Arm and Central Apparatus in Patients with Transposition of the Great Arteries.

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Fitzsimons L, Brewer V, Tucker K Cells. 2022; 11(12).

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