Identification and localization of TBX5 transcription factor during human cardiac morphogenesis

Mutations in the TBX5 transcription factor gene cause human cardiac malform ation in Holt-Gram syndrome. To identify and localize TBX5 during cardiac m orphogenesis, we performed immunohistochemical studies of TBX5 protein card iac expression during human embryogenesis. Specific antibody to human TBX5 was generated in rabbits with a TBX5 synthetic peptide and affinity purific ation of antiserum. Anti-TBX5 was used in immunohistochemical analyses of h uman cardiac tissue. In embryonic and adult heart, TBX5 is expressed throug hout the epicardium and in cardiomyocyte nuclei in myocardium of all four c ardiac chambers. Endocardial expression of TBX5 is only present in left ven tricle. Asymmetric left-sided transmyocardial gradients of TBX5 protein exp ression were observed in embryonic but not adult hearts. Human cardiac expr ession of TBX5 protein correlates with the cardiac manifestations of Holt-G ram syndrome. TBX5 transmyocardial protein gradients may contribute to norm al patterning of the human heart during embryogenesis. (C) 2000 Wiley-Liss, Inc.