Chamber-specific cardiac expression of Tbx5 and heart defects in Holt-Oramsyndrome

To further define the role of a T-box transcription factor, Tbx5, in cardia c development, we have examined its expression in the developing mouse and chick heart and correlated this pattern with cardiac defects caused by huma n TBX5 mutations in Holt-Gram syndrome. Early in the developing heart, Tbx5 is uniformly expressed throughout the entire cardiac crescent. Upon format ion of the linear heart tube, Tbx5 is expressed in a graded fashion, strong er near the posterior end and weaker at the anterior end. As the heart tube loop,asymmetric Tbx5 expression continues; Tbx5 is expressed in the presum ptive left ventricle, but not the right ventricle or outflow tract. This pa ttern of expression is maintained in more mature hearts. Expression in the ventricular septum is restricted to the left side and is contiguous with le ft ventricular free wall expression; Trabeculae, vena cavae (inferior and s uperior), and the atrial aspect of the atrioventricular valves also express high levels of Tbx5. These patterns of Tbx5 expression provide an embryolo gic basis for the prevalence of atrial septal defects (ostium primum and se cundum), ventricular muscular septal defects, and left-sided malformations (endocardial cushion defects, hypoplastic left heart, and aberrant trabecul ation) observed in patients with Holt-Gram syndrome. (C) 1999 Academic Pres s.