CFTR-β-catenin interaction regulates mouse embryonic stem cell differentiation and embryonic development.
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 β-catenin, defect of which leads to premature degradation of β-catenin and suppressed activation of β-catenin signaling. Furthermore, knockdown of CFTR retards the early development of Xenopus laevis with impaired mesoderm/endoderm differentiation and β-catenin signaling. Our study reveals a previously undefined role of CFTR in controlling ESC differentiation and early embryonic development via its interaction with β-catenin, and provides novel insights into the understanding of embryonic development.
Epithelial Cell Biology Research Center, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
Zhenqing
Z
Liu
Epithelial Cell Biology Research Center, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
Jinghui
J
Guo
Epithelial Cell Biology Research Center, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
Yan
Y
Wang
Epithelial Cell Biology Research Center, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
Zhihui
Z
Weng
Epithelial Cell Biology Research Center, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
Biao
B
Huang
Epithelial Cell Biology Research Center, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
Mei-Kuen
MK
Yu
Epithelial Cell Biology Research Center, The Chinese University of Hong Kong, Hong Kong SAR, PR China.|Sichuan University-The Chinese University of Hong Kong Joint Laboratory for Reproductive Medicine, West China Second University Hospital, Chengdu, PR China.
Xiaohu
0000-0002-5329-1599
X
Zhang
Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
Ping
P
Yuan
Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China.|School of Biomedical Sciences Core Laboratory, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, PR China.
Hui
H
Zhao
Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China.|School of Biomedical Sciences Core Laboratory, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, PR China.
Wai-Yee
WY
Chan
Epithelial Cell Biology Research Center, The Chinese University of Hong Kong, Hong Kong SAR, PR China.|Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China.|School of Biomedical Sciences Core Laboratory, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, PR China.
Xiaohua
X
Jiang
Epithelial Cell Biology Research Center, The Chinese University of Hong Kong, Hong Kong SAR, PR China.|Sichuan University-The Chinese University of Hong Kong Joint Laboratory for Reproductive Medicine, West China Second University Hospital, Chengdu, PR China.|Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China.|School of Biomedical Sciences Core Laboratory, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, PR China.
Hsiao-Chang
HC
Chan
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002712:Chlorides / Q000032:analysis; D005576:Colforsin / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004475:Ectoderm / Q000378:metabolism / Q000473:pathology; D004625:Embryo, Nonmammalian / Q000502:physiology; D047108:Embryonic Development; D004707:Endoderm / Q000378:metabolism / Q000473:pathology; D005260:Female; D008297:Male; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D000066450:Mouse Embryonic Stem Cells; D014157:Transcription Factors / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology; D060509:Wnt3A Protein / Q000378:metabolism; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000254:growth & development; D051176:beta Catenin / Q000378:metabolism*
D002712:Chlorides; D014157:Transcription Factors; D060509:Wnt3A Protein; D029867:Xenopus Proteins; D051176:beta Catenin; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin