CFTR-beta-catenin interaction regulates mouse embryonic stem cell differentiation and embryonic development

摘要

Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated anion channel capable of conducting both Cl(-)and HCO3-, mutations of which cause cystic fibrosis (CF), a common autosomal recessive disease. Although CF patients are known to have varied degree of developmental problems, the biological role of CFTR in embryonic development remains elusive. Here, we show that CFTR is functionally expressed in mouse ESCs. CFTR-/- mESCs exhibit dramatic defect in mesendoderm differentiation. In addition, CFTR physically interacts with beta-catenin, defect of which leads to premature degradation of beta-catenin and suppressed activation of beta- catenin signaling. Furthermore, knockdown of CFTR retards the early development of Xenopus laevis with impaired mesoderm/endoderm differentiation and beta-catenin signaling. Our study reveals a previously undefined role of CFTR in controlling ESC differentiation and early embryonic development via its interaction with beta-catenin, and provides novel insights into the understanding of embryonic development.