Abstract
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.
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Abbreviations
- CFTR:
-
cystic fibrosis transmembrane conductance regulator
- CF:
-
cystic fibrosis
- ESC:
-
embryonic stem cells
- ME:
-
mesendoderm
- MQAE:
-
N-ethoxycarbonylmethyl-6-methoxyquinolinium bromide
- WT:
-
wild-type
- KO:
-
knock-out
- EB:
-
embryoid body
- MO:
-
morpholino
- LIF:
-
leukemia inhibitory factor
- Axin:
-
Axis inhibition protein
- Ccnd1:
-
cyclin-D1
- CHIR99021:
-
mitogen-activated protein kinase inhibitor
- ERK:
-
extracellular-signal-regulated kinases
- GATA4:
-
GATA-binding protein 4
- GATA6:
-
GATA-binding protein 6
- GSC:
-
Goosecoid
- GSK3β:
-
glycogen synthase kinase 3β
- LEF1:
-
lymphoid enhancer-binding factor 1
- SSEA1:
-
stage-specific embryonic antigen-1
- T:
-
Brachyury
- TCF1:
-
hepatocyte nuclear factor 1 homeobox A
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Acknowledgements
This study was funded by National 973 Projects, grant numbers 2012CB944903 and 2013CB967401; National Science Foundation of China, grant numbers 31071019 and 31140034; Focused Investment Scheme of the Chinese University of Hong Kong; and Hong Kong University Grants Committee, grant numbers GRF/CUHK/466413 and 14119516.
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Liu, Z., Guo, J., Wang, Y. et al. CFTR- β -catenin interaction regulates mouse embryonic stem cell differentiation and embryonic development . Cell Death Differ 24, 98–110 (2017). https://doi.org/10.1038/cdd.2016.118
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DOI: https://doi.org/10.1038/cdd.2016.118
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