The Hippo pathway in tissue homeostasis and regeneration

Yu Wang, Aijuan Yu, Fa-Xing Yu

PDF(944 KB)
PDF(944 KB)
Protein Cell ›› 2017, Vol. 8 ›› Issue (5) : 349-359. DOI: 10.1007/s13238-017-0371-0
REVIEW
REVIEW

The Hippo pathway in tissue homeostasis and regeneration

Author information +
History +

Abstract

While several organs in mammals retain partial regenerative capability following tissue damage, the underlying mechanisms remain unclear. Recently, the Hippo signaling pathway, better known for its function in organ size control, has been shown to play a pivotal role in regulating tissue homeostasis and regeneration. Upon tissue injury, the activity of YAP, the major effector of the Hippo pathway, is transiently induced, which in turn promotes expansion of tissue-resident progenitors and facilitates tissue regeneration. In this review, with a general focus on the Hippo pathway, we will discuss its major components, functions in stem cell biology, involvement in tissue regeneration in different organs, and potential strategies for developing Hippo pathwaytargeted regenerative medicines.

Keywords

Hippo / YAP / regeneration

Cite this article

Download citation ▾
Yu Wang, Aijuan Yu, Fa-Xing Yu. The Hippo pathway in tissue homeostasis and regeneration. Protein Cell, 2017, 8(5): 349‒359 https://doi.org/10.1007/s13238-017-0371-0

References

[1]
AylonY, SarverA, TovyA, AinbinderE, OrenM (2014) Lats2 is critical for the pluripotency and proper differentiation of stem cells.Cell Death Differ21:624–633
CrossRef Google scholar
[2]
AzzolinL, PancieraT, SoligoS, EnzoE, BicciatoS, DupontS, BresolinS, FrassonC, BassoG, GuzzardoV (2014) YAP/TAZ incorporation in the β-catenin destruction complex orchestrates the Wnt response.Cell158:157–170
CrossRef Google scholar
[3]
BaiH, ZhangN, XuY, ChenQ, KhanM, PotterJJ, NayarSK, CornishT, AlpiniG, BronkS (2012) Yes-associated protein regulates the hepatic response after bile duct ligation.Hepatology56:1097–1107
CrossRef Google scholar
[4]
BarkerN (2014) Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration.Nat Rev Mol Cell Bio15:19–33
CrossRef Google scholar
[5]
BarryER, MorikawaT, ButlerBL, ShresthaK, de la RosaR, YanKS, FuchsCS, MagnessST, SmitsR, OginoS (2012) Restriction of intestinal stem cell expansion and the regenerative response by YAP.Nature493:106–110
CrossRef Google scholar
[6]
BenhamoucheS, CurtoM, SaotomeI, GladdenAB, LiuCH, GiovanniniM, McClatcheyAI (2010) Nf2/Merlin controls progenitor homeostasis and tumorigenesis in the liver.Genes Dev24:1718–1730
CrossRef Google scholar
[7]
BeyerTA, WeissA, KhomchukY, HuangK, OgunjimiAA, VarelasX, WranaJL (2013) Switch enhancers interpret TGF-β and Hippo signaling to control cell fate in human embryonic stem cells.Cell Rep5:1611–1624
CrossRef Google scholar
[8]
BondAM, MingG, SongH (2015) Adult mammalian neural stem cells and neurogenesis: five decades later.Cell Stem Cell17:385–395
CrossRef Google scholar
[9]
BorowiakM, WiglerMH (2004) Met provides essential signals for liver regeneration.Proc Natl Acad Sci USA101:10608–10613
CrossRef Google scholar
[10]
CaiJ, ZhangN, ZhengY, de WildeRF, MaitraA, PanD (2010) The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program.Genes Dev24:2383–2388
CrossRef Google scholar
[11]
CamargoFD, GokhaleS, JohnnidisJB, FuD, BellGW, JaenischR, BrummelkampTR (2007) YAP1 increases organ size and expands undifferentiated progenitor cells.Curr Biol17:2054–2060
CrossRef Google scholar
[12]
CaoX, PfaffSL, GageFH (2008) YAP regulates neural progenitor cell number via the TEA domain transcription factor.Genes Dev22:3320–3334
CrossRef Google scholar
[13]
CarlsonBM (2007) Principles of regenerative biology.Academic Press, Cambridge
[14]
ChenQ, ZhangN, XieR, WangW, CaiJ, ChoiKS, DavidKK, HuangB, YabutaN, NojimaH (2015) Homeostatic control of Hippo signaling activity revealed by an endogenous activating mutation in YAP.Genes Dev29:1285–1297
CrossRef Google scholar
[15]
ChungH, LeeBK, UpretyN, ShenW, LeeJ, KimJ (2016) Yap1 is dispensable for self-renewal but required for proper differentiation of mouse embryonic stem (ES) cells.Embo Rep17:519–529
CrossRef Google scholar
[16]
CleversH (2016) Modeling development and disease with organoids.Cell165:1586–1597
CrossRef Google scholar
[17]
CockburnK, BiecheleS, GarnerJ, RossantJ (2013) The hippo pathway member Nf2 Is required for inner cell mass specification.Curr Biol23:1195–1201
CrossRef Google scholar
[18]
CrosnierC, StamatakiD, LewisJ (2006) Organizing cell renewal in the intestine: stem cells, signals and combinatorial control.Nat Rev Genet7:349–359
CrossRef Google scholar
[19]
DelRe DP, YangY, NakanoN, ChoJ, ZhaiP, YamamotoT, ZhangN, YabutaN, NojimaH, PanD (2013) Yes-associated protein isoform 1 (Yap1) promotes cardiomyocyte survival and growth to protect against myocardial ischemic injury.J Biol Chem288:3977–3988
CrossRef Google scholar
[20]
DelreD, MatsudaT, ZhaiP, MaejimaY, JainMR, LiuT, LiH, HsuCP, SadoshimaJ (2014) Mst1 promotes cardiac myocyte apoptosis through phosphorylation and inhibition of Bcl-xL.Mol Cell54:639–650
CrossRef Google scholar
[21]
DingR, WeynansK, BossingT, BarrosCS, BergerC (2016) The Hippo signalling pathway maintains quiescence in Drosophila neural stem cells.Nat Commun7:10510
CrossRef Google scholar
[22]
DongJ, FeldmannG, HuangJ, WuS, ZhangN, ComerfordSA, GayyedMF, AndersRA, MaitraA, PanD (2007) Elucidation of a universal size-control mechanism in drosophila and mammals.Cell130:1120–1133
CrossRef Google scholar
[23]
ElbediwyA, Vincent-MistiaenZI, Spencer-DeneB, StoneRK, BoeingS, WculekSK, CorderoJ, TanEH, RidgwayR, BruntonVG (2016) Integrin signalling regulates YAP and TAZ to control skin homeostasis.Development143:1674–1687
CrossRef Google scholar
[24]
FanF, HeZ, KongLL, ChenQ, YuanQ, ZhangS, YeJ, LiuH, SunX, GengJ (2016) Pharmacological targeting of kinases MST1 and MST2 augments tissue repair and regeneration.Sci Transl Med8:108r–352r
CrossRef Google scholar
[25]
GjorevskiN, SachsN,ManfrinA,GigerS, BraginaME, Ordóñez-MoránP, CleversH, LutolfMP (2016) Designermatrices for intestinal stem cell and organoid culture.Nature539(7630):560–564
CrossRef Google scholar
[26]
GongR, YuFX (2015) Targeting the Hippo pathway for anti-cancer therapies.Curr Med Chem22:1
CrossRef Google scholar
[27]
GoodellMA, NguyenH, ShroyerN (2015) Somatic stem cell heterogeneity: diversity in the blood, skin and intestinal stem cell compartments.Nat Rev Mol Cell Biol16:299–309
CrossRef Google scholar
[28]
GregorieffA, LiuY, InanlouMR, KhomchukY, WranaJL (2015) Yapdependent reprogramming of Lgr5+ stem cells drives intestinal regeneration and cancer.Nature526:715–718
CrossRef Google scholar
[29]
GurtnerGC, SabineW, YannB, LongakerMT (2012) Wound repair and regeneration.Nature49:314–321
[30]
HalderG, JohnsonRL (2011) Hippo signaling: growth control and beyond.Development138:9–22
CrossRef Google scholar
[31]
HanM, YangX, FarringtonJE, MuneokaK (2003) Digit regeneration is regulated by Msx1 and BMP4 in fetal mice.Development130:5123–5132
CrossRef Google scholar
[32]
HeallenT, ZhangM, WangJ, Bonilla-ClaudioM, KlysikE, JohnsonRL, MartinJF (2011) Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size.Science332:458–461
CrossRef Google scholar
[33]
HeallenT, MorikawaY, LeachJ, TaoG, WillersonJT, JohnsonRL, MartinJF (2013) Hippo signaling impedes adult heart regeneration.Development140:4683–4690
CrossRef Google scholar
[34]
HirateY, HiraharaS, InoueK, SuzukiA, AlarconVB, AkimotoK, HiraiT, HaraT, AdachiM, ChidaK (2013) Polarity-dependent distribution of angiomotin localizes Hippo signaling in preimplantation embryos.Curr Biol23:1181–1194
CrossRef Google scholar
[35]
HuangZ, HuJ, PanJ, WangY, HuG, ZhouJ, MeiL, XiongW (2016) YAP stabilizes SMAD1 and promotes BMP2-induced neocortical astrocytic differentiation.Development143:2398–2409
CrossRef Google scholar
[36]
HuhCG, FactorVM, SánchezA, UchidaK, ConnerEA, ThorgeirssonSS (2004) Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair.Proc Natl Acad Sci USA101:4477–4482
CrossRef Google scholar
[37]
Iglesias-BartolomeR, TorresD, MaroneR, FengX, MartinD, SimaanM, ChenM, WeinsteinLS, TaylorSS, MolinoloAA (2015) Inactivation of a Gαs–PKA tumour suppressor pathway in skin stem cells initiates basal-cell carcinogenesis.Nat Cell Biol17:793–803
CrossRef Google scholar
[38]
ImajoM, EbisuyaM, NishidaE (2014) Dual role of YAP and TAZ in renewal of the intestinal epithelium.Nat Cell Biol17:7–19
CrossRef Google scholar
[39]
KarpowiczP, PerezJ, PerrimonN (2010) The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration.Development137:4135–4145
CrossRef Google scholar
[40]
KederA, Rives-QuintoN, AerneBL, FrancoM, TaponN, CarmenaA (2015) The Hippo pathway core cassette regulates asymmetric cell division.Curr Biol25:2739–2750
CrossRef Google scholar
[41]
KimKA, KakitaniM, ZhaoJ, OshimaT, TangT, BinnertsM, LiuY, BoyleB, ParkE, EmtageP (2005) Mitogenic influence of human R-spondin1 on the intestinal epithelium.Science309:1256–1259
CrossRef Google scholar
[42]
KorinekV, BarkerN, MoererP, VanDE, HulsG, PetersPJ, CleversH (1998) Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4.Nat Genet19:379–383
CrossRef Google scholar
[43]
LaflammeMA (2011) Heart regeneration.Nature473:326–335
CrossRef Google scholar
[44]
LaneSW, WilliamsDA, WattFM (2014) Modulating the stem cell niche for tissue regeneration.Nat Biotechnol32:795–803
CrossRef Google scholar
[45]
LavadoA, HeY, PareJ, NealeG, OlsonEN, GiovanniniM, CaoX (2013) Tumor suppressor Nf2 limits expansion of the neural progenitor pool by inhibiting Yap/Taz transcriptional coactivators.Development140:3323–3334
CrossRef Google scholar
[46]
LavadoA, WareM, PareJ, CaoX (2014) The tumor suppressor Nf2 regulates corpus callosum development by inhibiting the transcriptional coactivator Yap.Development141:4182–4193
CrossRef Google scholar
[47]
LeeJH, KimTS, YangTH, KooBK, OhSP, LeeKP, OhHJ, LeeSH, KongYY, KimJM(2008) A crucial role of WW45 in developing epithelial tissues in the mouse.Embo J27:1231–1242
CrossRef Google scholar
[48]
LeeKP, LeeJH, KimTS, KimTH, ParkHD, ByunJS, KimMC, JeongWI, CalvisiDF, KimJM (2010) The Hippo-Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis.Proc Natl Acad Sci USA107:8248–8253
CrossRef Google scholar
[49]
LeeD, ParkJO, KimT, KimS, KimT, KimM, ParkGS, KimJ, KuninakaS, OlsonEN (2016) LATS-YAP/TAZ controls lineage specification by regulating TGFβ signaling and Hnf4α expression during liver development.Nat Commun7:11961
CrossRef Google scholar
[50]
LiL, CleversH (2010) Coexistence of quiescent and active adult stem cells in mammals.Science327:542–545
CrossRef Google scholar
[51]
LiP, ChenY, MakKK, WongCK, WangCC, YuanP (2013) Functional role of Mst1/Mst2 in embryonic stem cell differentiation.PLoS ONE8:e79867
CrossRef Google scholar
[52]
LiQ, LiS, Mana-CapelliS, RothFR, DanaiLV, AmcheslavskyA, NieY, KanekoS, YaoX, ChenX (2014) The conserved misshapen-warts-Yorkie pathway acts in enteroblasts to regulate intestinal stem cells in Drosophila.Dev Cell31:291–304
CrossRef Google scholar
[53]
LianI, KimJ, OkazawaH, ZhaoJ, ZhaoB, YuJ, ChinnaiyanA, IsraelMA, GoldsteinLS, AbujarourR (2010) The role of YAP transcription coactivator in regulating stem cell self-renewal and differentiation.Genes Dev24:1106–1118
CrossRef Google scholar
[54]
LinZ, von GiseA, ZhouP, GuF, MaQ, JiangJ, YauAL, BuckJN, GouinKA, vanGorp PRR (2014) Cardiac-specific YAP activation improves cardiac function and survival in an experimental murine MI model.Circ Res115:354–363
CrossRef Google scholar
[55]
LinZ, GuoH, CaoY, ZohrabianS, ZhouP, MaQ, VanDusenN, GuoY, ZhangJ, StevensSM (2016) Acetylation of VGLL4 regulates Hippo-YAP signaling and postnatal cardiac growth.Dev Cell39:466–479
CrossRef Google scholar
[56]
LorthongpanichC, MesserschmidtDM, ChanSW, HongW, KnowlesBB, SolterD (2013) Temporal reduction of LATS kinases in the early preimplantation embryo prevents ICM lineage differentiation.Genes Dev27:1441–1446
CrossRef Google scholar
[57]
LuL, LiY, KimSM, BossuytW, LiuP, QiuQ, WangY, HalderG, FinegoldMJ, LeeJS(2010) Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver.Proc Natl Acad Sci USA107:1437–1442
CrossRef Google scholar
[58]
MatsuiY, NakanoN, ShaoD, GaoS, LuoW, HongC, ZhaiP, HolleE, YuX, YabutaN(2008) Lats2 Is a negative regulator of myocyte size in the heart.Circ Res103:1309–1318
CrossRef Google scholar
[59]
MiyajimaA, TanakaM, ItohT (2014) Stem/progenitor cells in liver development, homeostasis, regeneration, and reprogramming. Cell Stem Cell14:561–574
CrossRef Google scholar
[60]
MokalledMH, PatraC, DicksonAL, EndoT, StainierDY, PossKD (2016) Injury-induced ctgfa directs glial bridging and spinal cord regeneration in zebrafish.Science354:630–634
CrossRef Google scholar
[61]
MorikawaY, ZhangM, HeallenT, LeachJ, TaoG, XiaoY, BaiY, LiW, WillersonJT, MartinJF (2015) Actin cytoskeletal remodeling with protrusion formation is essential for heart regeneration in Hippodeficient mice.Sci Signal8:ra41
CrossRef Google scholar
[62]
MoroishiT, ParkHW, QinB, ChenQ, MengZ, PlouffeSW, TaniguchiK, YuFX, KarinM, PanD (2015) A YAP/TAZ-induced feedback mechanism regulates Hippo pathway homeostasis.Genes Dev29:1271–1284
CrossRef Google scholar
[63]
MoroishiT, HayashiT, PanWW, FujitaY, HoltMV, QinJ, CarsonDA, GuanKL (2016) The Hippo pathway kinases LATS1/2 suppress cancer immunity.Cell167:1525–1539
CrossRef Google scholar
[64]
OdashimaM, UsuiS, TakagiH, HongC, LiuJ, YokotaM, SadoshimaJ (2007) Inhibition of endogenous Mst1 prevents apoptosis and cardiac dysfunction without affecting cardiac hypertrophy after myocardial infarction.Circ Res100:1344–1352
CrossRef Google scholar
[65]
PanD (2010) The Hippo signaling pathway in development and cancer.Dev Cell19:491–505
CrossRef Google scholar
[66]
PancieraT, AzzolinL, FujimuraA, Di BiagioD, FrassonC, BresolinS, SoligoS, BassoG, BicciatoS, RosatoA (2016) Induction of expandable tissue-specific stem/progenitor cells through transient expression of YAP/TAZ.Cell Stem Cell19(6):725–737
CrossRef Google scholar
[67]
ParkR, MoonUY, ParkJY, HughesLJ, JohnsonRL, ChoS, KimS (2016) Yap is required for ependymal integrity and is suppressed in LPA-induced hydrocephalus.Nat Commun7:10329
CrossRef Google scholar
[68]
PoernbacherI, BaumgartnerR, MaradaSK, EdwardsK, StockerH (2012) Drosophila Pez acts in Hippo signaling to restrict intestinal stem cell proliferation.Curr Biol22:389–396
CrossRef Google scholar
[69]
PoitelonY, Lopez-AnidoC, CatignasK, BertiC, PalmisanoM, WilliamsonC, AmerosoD, AbikoK, HwangY, GregorieffA (2016) YAP and TAZ control peripheral myelination and the expression of laminin receptors in Schwann cells.Nat Neurosci19:879–887
CrossRef Google scholar
[70]
PoonCLC, MitchellKA, KondoS, ChengLY, HarveyKF (2016) The Hippo pathway regulates neuroblasts and brain size in Drosophila melanogaster.Curr Biol26:1034–1042
CrossRef Google scholar
[71]
PorrelloER, OlsonEN (2014) A neonatal blueprint for cardiac regeneration.Stem Cell Res13:556–570
CrossRef Google scholar
[72]
QianL, HuangY, SpencerCI, FoleyA, VedanthamV, LiuL, ConwaySJ, FuJD, SrivastavaD (2012) In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes.Nature485:593–598
CrossRef Google scholar
[73]
QinH, BlaschkeK, WeiG, OhiY, BlouinL, QiZ, YuJ, YehRF, HebrokM, Ramalho-SantosM (2012) Transcriptional analysis of pluripotency reveals the Hippo pathway as a barrier to reprogramming.Hum Mol Genet21:2054–2067
CrossRef Google scholar
[74]
QinH, HejnaM, LiuY, PerchardeM, WossidloM, BlouinL, Durruthy-DurruthyJ, WongP, QiZ, YuJ (2016) YAP induces human naive pluripotency.Cell Rep14:2301–2312
CrossRef Google scholar
[75]
ReddyBVVG, IrvineKD (2011) Regulation of Drosophila glial cell proliferation by Merlin–Hippo signaling.Development138:5201–5212
CrossRef Google scholar
[76]
RenF, WangB, YueT, YunEY, IpYT, JiangJ (2010) Hippo signaling regulates Drosophila intestine stem cell proliferation through multiple pathways.Proc Natl Acad Sci USA107:21064–21069
CrossRef Google scholar
[77]
RuizMM, RegueiroJR (2012) New tools in regenerative medicine: gene therapy.Springer, New York
[78]
SasakiH (2015) Position- and polarity-dependent Hippo signaling regulates cell fates in preimplantation mouse embryos.Semin Cell Dev Biol125:69–76
CrossRef Google scholar
[79]
SatoT, vanEs JH, SnippertHJ, StangeDE, VriesRG, VanDBM, BarkerN, ShroyerNF, VanDWM, CleversH (2011) Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts.Nature469:415–418
CrossRef Google scholar
[80]
SchlegelmilchK, MohseniM, KirakO, PruszakJ, RodriguezJR, ZhouD, KregerBT, VasioukhinV, AvruchJ, BrummelkampTR (2011) Yap1 acts downstream of alpha-catenin to control epidermal proliferation.Cell144:782–795
CrossRef Google scholar
[81]
ShaoD, ZhaiP, DelRe DP, SciarrettaS, YabutaN, NojimaH, LimD, PanD, SadoshimaJ (2014) A functional interaction between Hippo-YAP signalling and FoxO1 mediates the oxidative stress response.Nat Commun.
CrossRef Google scholar
[82]
ShawRL, KohlmaierA, PoleselloC, VeelkenC, EdgarBA, TaponN (2010) The Hippo pathway regulates intestinal stem cell proliferation during Drosophila adult midgut regeneration.Development137:4147–4158
CrossRef Google scholar
[83]
SolanasG, BenitahSA (2013) Regenerating the skin: a task for the heterogeneous stem cell pool and surrounding niche.Nat Rev Mol Cell Biol14:737–748
CrossRef Google scholar
[84]
SongH, MakKK, TopolL, YunK, HuJ, GarrettL, ChenY, ParkO, ChangJ, SimpsonRM (2010) Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppression.Proc Natl Acad Sci107:1431–1436
CrossRef Google scholar
[85]
SoudersCA, BowersSLK, BaudinoTA (2009) Cardiac fibroblast: the renaissance cell.Circ Res105:1164–1176
CrossRef Google scholar
[86]
StaleyBK, IrvineKD (2010) Warts and Yorkie mediate intestinal regeneration by influencing stem cell proliferation.Curr Biol20:1580–1587
CrossRef Google scholar
[87]
Stoick-CooperCL, MoonRT, WeidingerG (2007) Advances in signaling in vertebrate regeneration as a prelude to regenerative medicine.Genes Dev21:1292–1315
CrossRef Google scholar
[88]
SuT, BondarT, ZhouX, ZhangC, HeH, MedzhitovR (2015) Twosignal requirement for growth-promoting function of Yap in hepatocytes.eLife 4:e02948
CrossRef Google scholar
[89]
TammC, BöwerN, AnnerénC (2011) Regulation of mouse embryonic stem cell self-renewal by a Yes-YAP-TEAD2 signaling pathway downstream of LIF.J Cell Sci124:1136–1144
CrossRef Google scholar
[90]
TaoG, KahrPC, MorikawaY, ZhangM, RahmaniM, HeallenTR, LiL, SunZ, OlsonEN, AmendtBA (2016) Pitx2 promotes heart repair by activating the antioxidant response after cardiac injury.Nature534:119–123
CrossRef Google scholar
[91]
VarelasX, SakumaR, Samavarchi-TehraniP, PeeraniR, RaoBM, DembowyJ, YaffeMB, ZandstraPW, WranaJL (2008) TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal.Nat Cell Biol10:837–848
CrossRef Google scholar
[92]
von GiseA, LinZ, SchlegelmilchK, HonorLB, PanGM, BuckJN, MaQ, IshiwataT, ZhouB, CamargoFD (2012) YAP1, the nuclear target of Hippo signaling, stimulates heart growth through cardiomyocyte proliferation but not hypertrophy.Proc Natl Acad Sci USA109:2394–2399
CrossRef Google scholar
[93]
WhyteJL, SmithAA, HelmsJA (2012) Wnt Signaling and Injury Repair.Cold Spring Harb Perspect Biol4:409–422
CrossRef Google scholar
[94]
XinM, KimY, SutherlandLB, QiX, McanallyJ, SchwartzRJ, RichardsonJA, BasseldubyR, OlsonEN (2011) Regulation of insulin-like growth factor signaling by Yap governs cardiomyocyte proliferation and embryonic heart size.Sci Signal4:a70
CrossRef Google scholar
[95]
XinM, KimY, SutherlandLB, MurakamiM, QiX, McAnallyJ, PorrelloER, MahmoudAI, TanW, SheltonJM (2013) Hippo pathway effector Yap promotes cardiac regeneration.Proc Natl Acad Sci USA110:13839–13844
CrossRef Google scholar
[96]
YamamotoS, YangG, ZablockiD, LiuJ, HongC, KimS, SolerS, OdashimaM, ThaiszJ, YehiaG (2003) Activation of Mst1 causes dilated cardiomyopathy by stimulating apoptosis without compensatory ventricular myocyte hypertrophy.J Clin Invest111:1463–1474
CrossRef Google scholar
[97]
YiJ, LuL, YangerK, WangW, SohnBH, StangerBZ, ZhangM, MartinJF, AjaniJA, ChenJ (2016) Large tumor suppressor homologs 1 and 2 regulate mouse liver progenitor cell proliferation and maturation through antagonism of the coactivators YAP and TAZ.Hepatology64:1757–1772
CrossRef Google scholar
[98]
YimlamaiD, ChristodoulouC, GalliGG, YangerK, Pepe-MooneyB, GurungB, ShresthaK, CahanP, StangerBZ, CamargoFD (2014) Hippo pathway activity influences liver cell fate.Cell157:1324–1338
CrossRef Google scholar
[99]
YinH, KanastyRL, EltoukhyAA, VegasAJ, DorkinJR, AndersonDG (2014) Non-viral vectors for gene-based therapy.Nat Rev Genet15:541–555
CrossRef Google scholar
[100]
YinX, MeadBE, SafaeeH, LangerR, KarpJM, LevyO (2016) Engineering stem cell organoids.Cell Stem Cell18:25–38
CrossRef Google scholar
[101]
YuFX, GuanKL (2013) The Hippo pathway: regulators and regulations.Genes Dev27:355–371
CrossRef Google scholar
[102]
YuFX, ZhaoB, PanupinthuN, JewellJL, LianI, WangLH, ZhaoJ, YuanH, TumanengK, LiH (2012) Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling.Cell150:780–791
CrossRef Google scholar
[103]
YuFX, LuoJ, MoJS, LiuG, KimYC, MengZ, ZhaoL, PeymanG, OuyangH, JiangW(2014) Mutant Gq/11 promote uveal melanoma tumorigenesis by activating YAP.Cancer Cell25:822–830
CrossRef Google scholar
[104]
YuF, MengZ, PlouffeSW, GuanK (2015a) Hippo pathway regulation of gastrointestinal tissues.Annu Rev Physiol77:201–227
CrossRef Google scholar
[105]
YuFX, ZhaoB, GuanKL (2015b) Hippo pathway in organ size control, tissue homeostasis, and cancer.Cell163:811–828
CrossRef Google scholar
[106]
ZhangN, BaiH, DavidKK, DongJ, ZhengY, CaiJ, GiovanniniM, LiuP, AndersRA, PanD (2010) The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals.Dev Cell19:27–38
CrossRef Google scholar
[107]
ZhangH, PasolliHA, FuchsE (2011) Yes-associated protein (YAP) transcriptional coactivator functions in balancing growth and differentiation in skin.Proc Natl Acad Sci USA108:2270–2275
CrossRef Google scholar
[108]
ZhouD, ConradC, XiaF, ParkJS, PayerB (2009) Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene.Cancer Cell16:425–438
CrossRef Google scholar
[109]
ZhouD, ZhangY, WuH, BarryE, YinY, LawrenceE, DawsonD, WillisJE, MarkowitzSD, CamargoFD (2011) Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance.Proc Natl Acad Sci USA108:E1312–E1320
CrossRef Google scholar
[110]
ZhouQ, LiL, ZhaoB, GuanKL (2015) The Hippo pathway in heart development, regeneration, and diseases.Circ Res116:1431–1447
CrossRef Google scholar
[111]
ZiM, MaqsoodA, PreharS, MohamedTMA, Abou-LeisaR, RobertsonA, CartwrightEJ, RaySG, OhS, LimDS (2014) The mammalian Ste20-like kinase 2 (Mst2) modulates stress-induced cardiac hypertrophy.J Biol Chem289:24275–24288
CrossRef Google scholar

RIGHTS & PERMISSIONS

2017 The Author(s) 2017. This article is published with open access at Springerlink.com and journal.hep.com.cn
AI Summary AI Mindmap
PDF(944 KB)

Accesses

Citations

Detail

Sections
Recommended

/