Yap1/Taz are essential for the liver development in zebrafish
Yap1/Taz are essential for the liver development in zebrafish
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Yap1/Taz 对于斑马鱼肝脏发育至关重要
DOI：
10.1016/j.bbrc.2018.05.196
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发表时间：
2018-09-03
影响因子：
3.1
通讯作者：
Huang, Honghui
中科院分区：
文献类型：
--
作者：
Yi, Xiaogui;Yu, Jia;Huang, Honghui
Hippo通路调控细胞增殖和分化。yes相关蛋白（Yap）和带pdz结合基序的转录共激活因子（Taz）是Hippo通路的效应物。Yap/Taz在胚胎肝脏发育中的作用尚未见报道。本研究发现yap1和taz在斑马鱼胚胎的肝脏和其他消化器官中表达，并且在胚胎发生过程中，敲除yap1或taz不会导致明显的缺陷。有趣的是，Taz在yap1突变体中显著增加，这可能解释了他们正常发育的原因，尽管失去了yap1。然而,yap1 (- / -);Taz（+/-）胚胎的消化器官较小，一半以上的胚胎有双侧肝脏、胰腺和非环状肠。进一步分析发现，yap1（-/-）基因功能被破坏；taz（+/-）胚胎不影响肝芽的形成，但影响肝细胞增殖和邻近侧板中胚层（LPM）的运动。过表达野生型yap1或taz可挽救肝脏缺陷表型中的yap1(-/-)；taz（+/-）胚胎，表明Yap1与taz合作调节肝脏发育。此外，Yap1在肝脏发育中以tead依赖的方式发挥作用。我们的研究结果表明，Yap1/Taz调节LPM运动，促进细胞增殖，确保斑马鱼肝脏正常发育。(C) 2018爱思唯尔公司版权所有。
Hippo pathway regulates cell proliferation and differentiation. Yes-associated protein (Yap) and transcriptional coactivator with PDZ-binding motif (Taz) are effectors of Hippo pathway. The function of Yap/Taz in embryonic liver development has yet to be reported. Here yap1 and taz were found expressed in liver and other digestive organs in zebrafish embryos, and knockout of yap1 or taz did not lead to visible defects during embryogenesis. Interestingly, Taz was significantly increased in yap1 mutants, which may account for their normal development, albeit losing Yap1. However, yap1(-/-); taz(+/-) embryos exhibited smaller digestive organs, and more than half of them showed bilateral livers and pancreas and non-looped intestines. Further analysis revealed that the disrupted gene function in yap1(-/-); taz(+/-) embryos did not disturb liver bud formation, but instead impaired cell proliferation in liver and movement of the neighboring lateral plate mesoderm (LPM). Overexpression of wild type yap1 or taz could rescue the defective liver phenotypes in yap1(-/-); taz(+/-) embryos, indicating that Yap1 cooperate with Taz to regulate the liver development. In addition, Yap1 was found to function in a Tead-dependent manner in the liver development. Our results suggest that Yap1/Taz regulate LPM movement and promote cell proliferation to ensure proper liver development in zebrafish. (C) 2018 Elsevier Inc. All rights reserved.