SHROOM3 is downstream of the planar cell polarity pathway and loss-of-function results in congenital heart defects.

ABSTRACT: Congenital heart disease (CHD) is the most common birth defect, and the leading cause of death due to birth defects, yet causative molecular mechanisms remain mostly unknown. We previously implicated a novel CHD candidate gene, SHROOM3, in a patient with CHD. Using a Shroom3 gene trap knockout mouse (Shroom3^gt/gt) we demonstrate that SHROOM3 is downstream of the noncanonical Wnt planar cell polarity signaling pathway (PCP) and loss-of-function causes cardiac defects. We demonstrate Shroom3 expression within cardiomyocytes of the ventricles and interventricular septum from E10.5 onward, as well as within cardiac neural crest cells and second heart field cells that populate the cardiac outflow tract. We demonstrate that Shroom3^gt/gt mice exhibit variable penetrance of a

SUBMITTER: Durbin MD 

PROVIDER: S-EPMC8257046 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature