Continuous antagonism by Dkk1 counter activates canonical Wnt signaling and promotes cardiomyocyte differentiation of embryonic stem cells.

ABSTRACT: Embryonic stem (ES) cells give rise to mesodermal progenitors that differentiate to hematopoietic and cardiovascular cells. The wnt signaling pathway plays multiple roles in cardiovascular development through a network of intracellular effectors. To monitor global changes in wnt signaling during ES cell differentiation, we generated independent ES cell lines carrying the luciferase gene under promoters that uniquely respond to specific wnt pathway branches. Our results show that successive, mutually exclusive waves of noncanonical and canonical wnt signaling precede mesoderm differentiation. Blocking the initial noncanonical JNK/AP-1 signaling with SP60125 aborts cardiovascular differentiation and promotes hematopoiesis, whereas interference with the subsequent peak of canonical wnt signal

SUBMITTER: Rai M 

PROVIDER: S-EPMC3245675 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature