Activin receptor-like kinase 2 can mediate atrioventricular cushion transformation

Epithelial-mesenchymal transformation in the atrioventricular (AV) cushion of the tubular heart is a critical step in the formation of the valves and membranous septa. Transforming growth factor beta (TGF beta) ligands are a primary signal of this transformation. To investigate the expression and fu nction of specific Type I TGF beta receptors during AV cushion transformati on, we cloned and characterized the chicken homologues of two mammalian act ivin receptor-like kinases (ALK), ALK2 and ALK5, and generated specific, po lyclonal antibodies against the extracellular binding domains of each. Both the chicken ALK2 (ChALK2) and the chicken ALK5 (ChALK5) cDNAs encode prote ins that bind TGF beta 1 in the presence of the Type II TGF beta receptor. However, as expected, only ChALK5 stimulated the TGF beta-responsive PAI-1 promoter. These data establish that ChALK2 and ChALK5 are thf chicken homol ogues of the mammalian receptors ALK2 and ALK5. Both ChALK2 and ChALK5 are expressed by AV endocardial cells. AV cushion explants harvested from stage 13-18 embryos were incubated with antisera to ChALK2 or ChALK5. Anti-ChALK 2 antisera inhibited mesenchyme formation by 34-50% while neutralizing anti -ChALK5 antisera were without effect. These data demonstrate that ChALK2 ca n mediate transformation in the AV cushion. (C) 2000 Academic Press.