Requirement of Osr1 in second heart field (SHF) for proper outflow tract (OFT) alignment

Abstract

Congenital heart disease (CHD) is current in 1/3 of all birth defects and has the prevalence of 1 in 1000 births.1 1/3 of all CHDs consist of cardiac outflow tract (OFT) defects.1 Despite its high prevalence, the genetic ontogeny of CHD has much to be studied. Knocking out Osr1, a gene encoding for a putative transcription factor containing four C2H2-type zinc finger motifs, is reported to cause heart defects including atrioventricular septal defects (AVSDs) in mice2-4 while its involvement in OFT development has yet to be studied. Osr1 is expressed in the second heart field (SHF), overlapping the expression of Gli1, an important modulator of sonic hedgehog (Shh) signaling pathway.4 Shh-signaling has been reported to contribute to the OFT development.5 Our preliminary study has shown that Osr1 deletion causes OFT defects including DORV and OA—suggesting its role in OFT alignment. We hypothesize that Osr1 is required in the SHF and Shh-signaling for proper OFT alignment. We will use a Cre-lox cell-specific KO technique to create embryos with Osr1 specific KO in SHF cells and Shh-receiving cells. We expect to observe high percentages of OFT misalignment including DORV and OA in embryos with Osr1 specific KO in SHF cells and Shh-receiving cells. This study will provide information which cell lineage is required for Osr1 in OFT development.