Disrupted development of the cardiac valves - structures that ensure unidirectional blood flow through the heart - causes about a third of human congenital heart defects. The signals that regulate endocardial epithelial-mesenchymal transformation (EMT), an early stage of cardiac valve development, are well understood, but what regulates the later stages of this important developmental process? On , Chen-Leng Cai and colleagues report that the T-box transcription factor Tbx20 is expressed in mouse endocardial cushions and valves throughout their development. They show that endocardial Tbx20 expression is not essential for EMT initiation but is required for endocardial cushion maturation and valve elongation in mice. Mechanistically, Tbx20 regulates Lef1 (a transcriptional regulator of Wnt/β-catenin signalling) in cushion endocardial cells, and disruption of Tbx20 expression leads to aberrant Wnt/β-catenin signalling in the endocardial cushions. Thus, the researchers conclude, Tbx20 acts upstream of Wnt signalling to regulate late steps in cardiac valve formation, a finding that provides new insights into the aetiology of human cardiac valve defects.
