Journal
CELLULAR SIGNALLING
Volume 27, Issue 3, Pages 578-586Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2014.12.013
Keywords
Enteric nervous system; NEDI2; GDNF/Ret signaling; Mouse
Categories
Funding
- Chinese National Basic Research Programs [2012CB910304, 2011CB910602]
- Chinese National Natural Science Foundation [31125010, 81221004, 31471364]
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Although glial cell line-derived neurotrophic factor (GDNF)/Ret signaling is essential for enteric nervous system (ENS) development, the positive regulators regulating GDNF/Ret signaling and controlling ENS development are poorly understood. Here, we show that Nedd4-related E3 ubiquitin ligase-2 (NEDL2) plays an essential and positive physiological role in regulating ENS development and GDNF/Ret signaling. All of the NEDL2-deficient mice die within 2 weeks after birth, showing low body weight. These mice showed a progressive bowel motility defect resulting from intestinal aganglionosis. We show that NEDL2 positively regulates enteric neural precursor proliferation through the GDNF/Akt signaling pathway. Together, these findings unveil the physiological function of NEDL2 in vivo. (C) 2014 Elsevier Inc. All rights reserved.
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