Cindy Rodrigues Cleto
Newcastle University, UK
Title: Defective cilia in endocardial derived cells; A cause for congenital heart defects?
Biography
Biography: Cindy Rodrigues Cleto
Abstract
Introduction: Primary cilia on endocardial cells could prove to be a cause of congenital heart defects. Endocardial cells mainly contribute to the outflow tract (OFT) and atrioventricular (AV) endocardial cushion; later developing into the four heart valves. Knocking out IFT88 creates abnormal primary cilia and in turn causes cardiac malformations.
Aims: The aims of this study were to establish the spatiotemporal expression of primary cilia on endocardial derived cells; and by using an IFT88 mouse model, to discover if defecting to the primary cilia in endocardial derived cells causes an abnormal cardiac phenotype?
Methods: For the spatiotemporal expression of primary cilia, Tie2Cre positive mouse embryos of age’s e10.5-e12.5 were stained with anti-green fluorescent protein and acetylated tubulin to show the endothelial cells and primary cilia respectively. For the IFT88 mouse model, three mutants were collects at e15.5; two were hematoxylin and eosin stained to look at histology and one was stained with acetylated tubulin to show any defect in the primary cilia.
Results: The spatiotemporal expression of primary cilia mainly highlighted that there is an abundance of cilia in the OFT and AV endocardial cushions at e10.5 and e11.5 but this significantly drops by e12.5. The IFT88 mouse model showed that knocking out IFT88 significantly decreases the number of primary cilia in mutants, causing cardiac malformations including atrio-ventricular septal defects and dysplastic mitral and tricuspid valves.
Conclusion: Primary cilia are present in the endocardial derived cells at earlier time points. Knocking out IFT88 does produce defective cilia that lead to cardiac malformations.
Aims: The aims of this study were to establish the spatiotemporal expression of primary cilia on endocardial derived cells; and by using an IFT88 mouse model, to discover if defecting to the primary cilia in endocardial derived cells causes an abnormal cardiac phenotype?
Methods: For the spatiotemporal expression of primary cilia, Tie2Cre positive mouse embryos of age’s e10.5-e12.5 were stained with anti-green fluorescent protein and acetylated tubulin to show the endothelial cells and primary cilia respectively. For the IFT88 mouse model, three mutants were collects at e15.5; two were hematoxylin and eosin stained to look at histology and one was stained with acetylated tubulin to show any defect in the primary cilia.
Results: The spatiotemporal expression of primary cilia mainly highlighted that there is an abundance of cilia in the OFT and AV endocardial cushions at e10.5 and e11.5 but this significantly drops by e12.5. The IFT88 mouse model showed that knocking out IFT88 significantly decreases the number of primary cilia in mutants, causing cardiac malformations including atrio-ventricular septal defects and dysplastic mitral and tricuspid valves.
Conclusion: Primary cilia are present in the endocardial derived cells at earlier time points. Knocking out IFT88 does produce defective cilia that lead to cardiac malformations.