The Hippo Signaling Pathway in Regenerative Medicine

  • Lixin Hong
  • Yuxi Li
  • Qingxu Liu
  • Qinghua Chen
  • Lanfen Chen
  • Dawang ZhouEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1893)


The major role of Hippo signaling is to inhibit their downstream effectors YAP/TAZ for organ size control during development and regeneration (Nat Rev Drug Discov 13(1):63–79, 2014; Dev Cell 19(4):491–505, 2010; Cell 163(4):811–828, 2015). We and others have demonstrated that the genetic disruption of kinases Mst1 and Mst2 (Mst1/2), the core components of Hippo signaling, results in YAP activation and sustained liver growth, thereby leading to an eight- to tenfold increase in liver size within 3 months and occurrence of liver cancer within 5 months (Curr Biol 17(23):2054–2060, 2007; Cancer Cell 16(5):425–438, 2009; Cell 130(6):1120–1133, 2007; Cancer Cell 31(5):669–684 e667, 2017; Nat Commun 6:6239, 2015; Cell Rep 3(5):1663–1677, 2013). XMU-MP-1, an Mst1/2 inhibitor, is able to augment mouse liver and intestinal repair and regeneration in both acute and chronic injury mouse models (Sci Transl Med 8:352ra108, 2016).In addition, YAP-deficient mice show an impaired intestinal regenerative response after DSS treatment or gamma irradiation (Proc Natl Acad Sci U S A 108(49):E1312–1320, 2011; Nature 493(7430):106–110, 2013; Genes Dev 24(21):2383–2388, 2010; J Vis Exp (111), 2010). IBS008738, a TAZ activator, facilitates muscle repair after cardiotoxin-induced muscle injury (Mol Cell Biol. 2014;34(9):1607–21). Deletion of Salvador (Sav) in mouse hearts enhances cardiomyocyte regeneration with reduced fibrosis and recovery of pumping function after myocardial infarction (MI) or resection of mouse cardiac apex (Development 140(23):4683–4690, 2013; Sci Signal 8(375):ra41, 2015; Nature 550(7675):260–264, 2017). This chapter provides a detailed description of procedures and important considerations when performing the protocols for the respective assays used to determine the effects of Hippo signaling on tissue repair and regeneration.

Key words

Hippo signaling Tissue regeneration Protocol 



The authors thank Quan Yuan (Xiamen University, China) for critical reading of the protocol of FRG mice model. This work was supported by grants from National Key R&D Program of China 2017YFA0504502 to D.Z. and L.C., the National Natural Science Foundation of China (81790254, 31625010, and U1505224 to D.Z.; U1405225 and 81372617 to L.C.; and 81472229 to L.H.). Lixin Hong and Yuxi Li contributed equally to this work.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Lixin Hong
    • 1
  • Yuxi Li
    • 1
  • Qingxu Liu
    • 1
  • Qinghua Chen
    • 1
  • Lanfen Chen
    • 1
  • Dawang Zhou
    • 1
    Email author
  1. 1.State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life SciencesXiamen UniversityXiamenChina

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