Dev106518 1..10

The identification and characterization of the cellular and molecular pathways involved in the differentiation andmorphogenesis of specific cell types of the developing heart are crucial to understanding the process of cardiac development and the pathology associated with human congenital heart disease. Here, we show that the cardiac transcription factorCASTOR(CASZ1)directly interactswithcongenital heart disease 5 protein (CHD5), which is also known as tryptophanrich basic protein (WRB), a gene located on chromosome 21 in the proposed region responsible forcongenital heart disease in individuals with Down’s syndrome.Wedemonstrate that loss ofCHD5 inXenopus leads to compromised myocardial integrity, improper deposition of basement membrane, and a resultant failure of hearts to undergo cell movements associated with cardiac formation. We further report that CHD5 is essential for CASZ1 function and that the CHD5-CASZ1 interaction is necessary forcardiacmorphogenesis.Collectively, these results establish a role for CHD5 and CASZ1 in the early stages of vertebrate cardiac development.