Activin receptor-like kinase 2 can mediate atrioventricular cushion transformation.

Lai YT, Beason KB, Brames GP, Desgrosellier JS, Cleggett MC, Shaw MV, Brown CB, Barnett JV
Dev Biol. 2000 222 (1): 1-11

PMID: 10885742 · DOI:10.1006/dbio.2000.9698

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 (TGFbeta) ligands are a primary signal of this transformation. To investigate the expression and function of specific Type I TGFbeta receptors during AV cushion transformation, we cloned and characterized the chicken homologues of two mammalian activin receptor-like kinases (ALK), ALK2 and ALK5, and generated specific, polyclonal antibodies against the extracellular binding domains of each. Both the chicken ALK2 (ChALK2) and the chicken ALK5 (ChALK5) cDNAs encode proteins that bind TGFbeta1 in the presence of the Type II TGFbeta receptor. However, as expected, only ChALK5 stimulated the TGFbeta-responsive PAI-1 promoter. These data establish that ChALK2 and ChALK5 are the chicken homologues 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-ChALK2 antisera inhibited mesenchyme formation by 34-50% while neutralizing anti-ChALK5 antisera were without effect. These data demonstrate that ChALK2 can mediate transformation in the AV cushion.

MeSH Terms (15)

Activin Receptors, Type II Amino Acid Sequence Animals Atrioventricular Node Base Sequence Chick Embryo COS Cells DNA, Complementary DNA Primers Immune Sera Molecular Sequence Data Morphogenesis Protein-Serine-Threonine Kinases Receptors, Growth Factor Sequence Homology, Amino Acid

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