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NEDL2 is an essential regulator of enteric neural development and GDNF/ Ret signaling

机译:NEDL2是肠神经发育和GDNF / Ret信号传导的重要调节剂

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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.
机译:尽管神经胶质细胞源性神经营养因子(GDNF)/ Ret信号对于肠神经系统(ENS)的发育至关重要,但是对调节GDNF / Ret信号和控制ENS发育的正调节剂知之甚少。在这里,我们显示Nedd4相关的E3泛素连接酶2(NEDL2)在调节ENS发育和GDNF / Ret信号传导中起着至关重要的积极作用。所有NEDL2缺陷型小鼠均在出生后2周内死亡,表明体重低。这些小鼠表现出由肠神经节病引起的进行性肠蠕动缺陷。我们表明,NEDL2积极调节通过GDNF / Akt信号通路的肠神经前体增殖。这些发现共同揭示了NEDL2在体内的生理功能。 (C)2014 Elsevier Inc.保留所有权利。

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