The Merlin/NF2 Tumor Suppressor Functions through the YAP Oncoprotein to Regulate Tissue Homeostasis in Mammals
Open accessAbstract
The conserved Hippo signaling pathway regulates organ size in Drosophila and mammals. While a core kinase cascade leading from the protein kinase Hippo (Hpo) (Mst1 and Mst2 in mammals) to the transcription coactivator Yorkie (Yki) (YAP in mammals) has been established, upstream regulators of the Hippo kinase cascade are less well defined, especially in mammals. Using conditional knockout mice, we demonstrate that the Merlin/NF2 tumor suppressor and the YAP oncoprotein function antagonistically to regulate liver development. While inactivation of Yap led to loss of hepatocytes and biliary epithelial cells, inactivation of Nf2 led to hepatocellular carcinoma and bile duct hamartoma. Strikingly, the Nf2-deficient phenotypes in multiple tissues were largely suppressed by heterozygous deletion of Yap, suggesting that YAP is a major effector of Merlin/NF2 in growth regulation. Our studies link Merlin/NF2 to mammalian Hippo signaling and implicate YAP activation as a mediator of pathologies relevant to Neurofibromatosis 2.
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Loss of Nf2 or Lats1/2 forces hepatocytes to commit to the BEC lineage.
“Additionally, loss of Nf2 or Lats1/2 forces hepatocytes to commit to the BEC lineage14,15.”
From HBO1 functions as an epigenetic barrier to hepatocyte plasticity and reprogramming during liver injury (2025) · cites this paper as [15]
The Results section, “Loss of NF2 leads to hepatocyte and biliary epithelium overproliferation” (page unavailable), reports excess BECs after Nf2 deletion, but describes the proliferating cells as being of biliary origin; it does not show hepatocytes committing to the BEC lineage. The Results section, “NF2 is required for Hippo signaling” (page unavailable), reports reduced Lats1/2 activity in Nf2-deficient livers, not the effect of deleting Lats1/2. (LLM, conf=0.86)
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Tuveson, D. A., Shaw, A. T., Willis, N. A., Silver, D. P., Jackson, E. L., Chang, S., Mercer, K. L., Grochow, R., Hock, H., Crowley, D., et al. (2004) · Cancer Cell · doi:10.1016/s1535-6108(04)00085-6 · Cited by 798 · see citing works
Wu, S., Liu, Y., Zheng, Y., Dong, J., & Pan, D. (2008) · Developmental Cell · doi:10.1016/j.devcel.2008.01.007 · Cited by 640 · see citing works
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- Baumgartner R Poernbacher I Buser N Hafen E Stocker H The WW domain protein Kibra acts upstream of hippo in Drosophila Dev. Cell 2010 18 309 316 20159600
- Bennett FC Harvey KF Fat cadherin modulates organ size in Drosophila via the Salvador/Warts/Hippo signaling pathway Curr. Biol 2006 16 2101 2110 17045801
- Bouzas EA Freidlin V Parry DM Eldridge R Kaiser-Kupfer MI Lens opacities in neurofibromatosis 2: further significant correlations Br. J. Ophthalmol 1993 77 354 357 8318482 PMC504529
- Calera MR Topley HL Liao Y Duling BR Paul DL Goodenough DA Connexin43 is required for production of the aqueous humor in the murine eye J. Cell Sci 2006 119 4510 4519 17046998
- Camargo FD Gokhale S Johnnidis JB Fu D Bell GW Jaenisch R Brummelkamp TR YAP1 increases organ size and expands undifferentiated progenitor cells Curr. Biol 2007 17 2054 2060 17980593
- Cang Y Zhang J Nicholas SA Bastien J Li B Zhou P Goff SP Deletion of DDB1 in mouse brain and lens leads to p53-dependent elimination of proliferating cells Cell 2006 127 929 940 17129780
- Cho E Feng Y Rauskolb C Maitra S Fehon R Irvine KD Delineation of a Fat tumor suppressor pathway Nat. Genet 2006 38 1142 1150 16980976
- Dong J Feldmann G Huang J Wu S Zhang N Comerford SA Gayyed MF Anders RA Maitra A Pan D Elucidation of a universal size-control mechanism in Drosophila and mammals Cell 2007 130 1120 1133 17889654 PMC2666353
- Evans DG Kalamarides M Hunter-Schaedle K Blakeley J Allen J Babovic-Vuskanovic D Belzberg A Bollag G Chen R DiTomaso E Golfinos J Harris G Jacob A Kalpana G Karajannis M Korf B Kurzrock R Law M McClatchey A Packer R Roehm P Rubenstein A Slattery W III Tonsgard JH Welling DB Widemann B Yohay K Giovannini M Consensus recommendations to accelerate clinical trials for neurofibromatosis type 2 Clin. Cancer Res 2009 15 5032 5039 19671848 PMC4513640
- Feng Y Irvine KD Processing and phosphorylation of the Fat receptor Proc. Natl. Acad. Sci. U. S. A 2009 106 11989 11994 19574458 PMC2709664
- Geisler F Nagl F Mazur PK Lee M Zimber-Strobl U Strobl LJ Radtke F Schmid RM Siveke JT Liver-specific inactivation of Notch2, but not Notch1, compromises intrahepatic bile duct development in mice Hepatology 2008 48 607 616 18666240
- Genevet A Wehr MC Brain R Thompson BJ Tapon N Kibra is a regulator of the Salvador/Warts/Hippo signaling network Dev. Cell 2010 18 300 308 20159599 PMC2845807
- Giovannini M Robanus-Maandag E van d. V Niwa-Kawakita M Abramowski V Goutebroze L Woodruff JM Berns A Thomas G Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2 Genes Dev 2000 14 1617 1630 10887156 PMC316733
- Goulev Y Fauny JD Gonzalez-Marti B Flagiello D Silber J Zider A SCALLOPED interacts with YORKIE, the nuclear effector of the hippo tumor-suppressor pathway in Drosophila Curr. Biol 2008 18 435 441 18313299
- Grzeschik NA Parsons LM Allott ML Harvey KF Richardson HE Lgl, aPKC, and Crumbs regulate the Salvador/Warts/Hippo pathway through two distinct mechanisms Curr. Biol 2010 20 573 581 20362447
- Hamaratoglu F Willecke M Kango-Singh M Nolo R Hyun E Tao C Jafar-Nejad H Halder G The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis Nat. Cell Biol 2006 8 27 36 16341207
- Harvey KF Pfleger CM Hariharan IK The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis Cell 2003 114 457 467 12941274
- Huang J Wu S Barrera J Matthews K Pan D The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP Cell 2005 122 421 434 16096061
- Jia J Zhang W Wang B Trinko R Jiang J The Drosophila Ste20 family kinase dMST functions as a tumor suppressor by restricting cell proliferation and promoting apoptosis Genes Dev 2003 17 2514 2519 14561774 PMC218145
- Justice RW Zilian O Woods DF Noll M Bryant PJ The Drosophila tumor suppressor gene warts encodes a homolog of human myotonic dystrophy kinase and is required for the control of cell shape and proliferation Genes Dev 1995 9 534 546 7698644
- Kango-Singh M Nolo R Tao C Verstreken P Hiesinger PR Bellen HJ Halder G Shar-pei mediates cell proliferation arrest during imaginal disc growth in Drosophila Development 2002 129 5719 5730 12421711
- Kreamer BL Staecker JL Sawada N Sattler GL Hsia MT Pitot HC Use of a low-speed, iso-density percoll centrifugation method to increase the viability of isolated rat hepatocyte preparations In Vitro Cell Dev. Biol 1986 22 201 211 2871008
- Lai ZC Wei X Shimizu T Ramos E Rohrbaugh M Nikolaidis N Ho LL Li Y Control of Cell Proliferation and Apoptosis by Mob as Tumor Suppressor, Mats Cell 2005 120 675 685 15766530
- LaJeunesse DR McCartney BM Fehon RG Structural analysis of Drosophila merlin reveals functional domains important for growth control and subcellular localization J. Cell Biol 1998 141 1589 1599 9647651 PMC2133006
- Lemaigre FP Development of the biliary tract Mech. Dev 2003 120 81 87 12490298
- Li W You L Cooper J Schiavon G Pepe-Caprio A Zhou L Ishii R Giovannini M Hanemann CO Long SB Erdjument-Bromage H Zhou P Tempst P Giancotti FG Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus Cell 2010 140 477 490 20178741 PMC2828953
- Ling C Zheng Y Yin F Yu J Huang J Hong Y Wu S Pan D The apical transmembrane protein Crumbs functions as a tumor suppressor that regulates Hippo signaling by binding to Expanded Proc. Natl. Acad. Sci. U. S. A 2010 PMC2890787 20498073
- Liu P Jenkins NA Copeland NG A highly efficient recombineering-based method for generating conditional knockout mutations Genome Res 2003 13 476 484 12618378 PMC430283
- Lu L Li Y Kim SM Bossuyt W Liu P Qiu Q Wang Y Halder G Finegold MJ Lee JS Johnson RL Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver Proc. Natl. Acad. Sci. U. S. A 2010 107 1437 1442 20080689 PMC2824398
- Maitra S Kulikauskas RM Gavilan H Fehon RG The tumor suppressors Merlin and Expanded function cooperatively to modulate receptor endocytosis and signaling Curr. Biol 2006 16 702 709 16581517
- Mao Y Rauskolb C Cho E Hu WL Hayter H Minihan G Katz FN Irvine KD Dachs: an unconventional myosin that functions downstream of Fat to regulate growth, affinity and gene expression in Drosophila Development 2006 133 2539 2551 16735478
- McClatchey AI Giovannini M Membrane organization and tumorigenesis--the NF2 tumor suppressor, Merlin Genes Dev 2005 19 2265 2277 16204178
- McClatchey AI Saotome I Ramesh V Gusella JF Jacks T The Nf2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation Genes Dev 1997 11 1253 1265 9171370
- Morin-Kensicki EM Boone BN Howell M Stonebraker JR Teed J Alb JG Magnuson TR O'Neal W Milgram SL Defects in yolk sac vasculogenesis, chorioallantoic fusion, and embryonic axis elongation in mice with targeted disruption of Yap65 Mol. Cell Biol 2006 26 77 87 16354681 PMC1317614
- Nakanuma Y Ohta G Immunohistochemical study on bile ductular proliferation in various hepatobiliary diseases Liver 1986 6 205 211 2430163
- Oh H Irvine KD In vivo regulation of Yorkie phosphorylation and localization Development 2008 135 1081 1088 18256197 PMC2387210
- Okada T You L Giancotti FG Shedding light on Merlin's wizardry Trends Cell Biol 2007 17 222 229 17442573
- Overholtzer M Zhang J Smolen GA Muir B Li W Sgroi DC Deng CX Brugge JS Haber DA Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon Proc. Natl. Acad. Sci. U. S. A 2006 103 12405 12410 16894141 PMC1533802
- Pantalacci S Tapon N Leopold P The Salvador partner Hippo promotes apoptosis and cell-cycle exit in Drosophila Nat. Cell Biol 2003 5 921 927 14502295
- Pellock BJ Buff E White K Hariharan IK The Drosophila tumor suppressors Expanded and Merlin differentially regulate cell cycle exit, apoptosis, and Wingless signaling Dev. Biol 2006 PMC1924969 17258190
- Praskova M Xia F Avruch J MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation Curr. Biol 2008 18 311 321 18328708 PMC4682548
- Robinson BS Huang J Hong Y Moberg KH Crumbs regulates Salvador/Warts/Hippo signaling in Drosophila via the FERM-domain protein expanded Curr. Biol 2010 20 582 590 20362445 PMC2855393
- Silva E Tsatskis Y Gardano L Tapon N McNeill H The tumor-suppressor gene fat controls tissue growth upstream of expanded in the hippo signaling pathway Curr. Biol 2006 16 2081 2089 16996266
- Song H Mak KK Topol L Yun K Hu J Garrett L Chen Y Park O Chang J Simpson RM Wang CY Gao B Jiang J Yang Y Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppression Proc. Natl. Acad. Sci. U. S. A 2010 107 1431 1436 20080598 PMC2824397
- Sopko R Silva E Clayton L Gardano L Barrios-Rodiles M Wrana J Varelas X Arbouzova NI Shaw S Saburi S Matakatsu H Blair S McNeill H Phosphorylation of the tumor suppressor fat is regulated by its ligand Dachsous and the kinase discs overgrown Curr. Biol 2009 19 1112 1117 19540118 PMC2851237
- Tapon N Harvey KF Bell DW Wahrer DC Schiripo TA Haber DA Hariharan IK salvador Promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines Cell 2002 110 467 478 12202036
- Tyler DM Baker NE Expanded and fat regulate growth and differentiation in the Drosophila eye through multiple signaling pathways Dev. Biol 2007 305 187 201 17359963 PMC2075468
- Udan RS Kango-Singh M Nolo R Tao C Halder G Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathway Nat. Cell Biol 2003 5 914 920 14502294
- Wei X Shimizu T Lai ZC Mob as tumor suppressor is activated by Hippo kinase for growth inhibition in Drosophila EMBO J 2007 26 1772 1781 17347649 PMC1847660
- Willecke M Hamaratoglu F Kango-Singh M Udan R Chen CL Tao C Zhang X Halder G The fat cadherin acts through the hippo tumor-suppressor pathway to regulate tissue size Curr. Biol 2006 16 2090 2100 16996265
- Wu S Huang J Dong J Pan D hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts Cell 2003 114 445 456 12941273
- Xu T Wang W Zhang S Stewart RA Yu W Identifying tumor suppressors in genetic mosaics: The Drosophila lats gene encodes a putative protein kinase Development 1995 121 1053 1063 7743921
- Xu X Kobayashi S Qiao W Li C Xiao C Radaeva S Stiles B Wang RH Ohara N Yoshino T LeRoith D Torbenson MS Gores GJ Wu H Gao B Deng CX Induction of intrahepatic cholangiocellular carcinoma by liver-specific disruption of Smad4 and Pten in mice J. Clin. Invest 2006 116 1843 1852 16767220 PMC1474816
- Yu J Zheng Y Dong J Klusza S Deng WM Pan D Kibra functions as a tumor suppressor protein that regulates hippo signaling in conjunction with Merlin and expanded Dev. Cell 2010 18 288 299 20159598 PMC2858562
- Zender L Spector MS Xue W Flemming P Cordon-Cardo C Silke J Fan ST Luk JM Wigler M Hannon GJ Mu D Lucito R Powers S Lowe SW Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach Cell 2006 125 1253 1267 16814713 PMC3026384
- Zhang L Ren F Zhang Q Chen Y Wang B Jiang J The TEAD/TEF family of transcription factor Scalloped mediates Hippo signaling in organ size control Dev. Cell 2008 14 377 387 18258485 PMC2292673
- Zhao B Wei X Li W Udan RS Yang Q Kim J Xie J Ikenoue T Yu J Li L Zheng P Ye K Chinnaiyan A Halder G Lai ZC Guan KL Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control Genes Dev 2007 21 2747 2761 17974916 PMC2045129
- Zhou D Conrad C Xia F Park JS Payer B Yin Y Lauwers GY Thasler W Lee JT Avruch J Bardeesy N Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene Cancer Cell 2009 16 425 438 19878874 PMC3023165
- Zong Y Panikkar A Xu J Antoniou A Raynaud P Lemaigre F Stanger BZ Notch signaling controls liver development by regulating biliary differentiation Development 2009 136 1727 1739 19369401 PMC2673761
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Yu, F.-X., Zhao, B., & Guan, K.-L. (2015) · Cell · doi:10.1016/j.cell.2015.10.044 · Cited by 2,206 · see citing works
YAP/TAZ at the Roots of Cancer
Zanconato, F., Cordenonsi, M., & Piccolo, S. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.05.005 · Cited by 1,970 · see citing works
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Meng, Z., Moroishi, T., & Guan, K.-L. (2016) · Genes & Development · doi:10.1101/gad.274027.115 · Cited by 1,667 · see citing works
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Yu, F.-X., Zhao, B., Panupinthu, N., Jewell, J. L., Lian, I., Wang, L. H., Zhao, J., Yuan, H., Tumaneng, K., Li, H., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.037 · Cited by 1,628 · see citing works
Liu-Chittenden, Y., Huang, B., Shim, J. S., Chen, Q., Lee, S.-J., Anders, R. A., Liu, J. O., & Pan, D. (2012) · Genes & Development · doi:10.1101/gad.192856.112 · Cited by 1,452 · see citing works
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Zanconato, F., Forcato, M., Battilana, G., Azzolin, L., Quaranta, E., Bodega, B., Rosato, A., Bicciato, S., Cordenonsi, M., & Piccolo, S. (2015) · Nature Cell Biology · doi:10.1038/ncb3216 · Cited by 1,219 · see citing works
The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal
Zhao, B., Tumaneng, K., & Guan, K.-L. (2011) · Nature Cell Biology · doi:10.1038/ncb2303 · Cited by 1,205 · see citing works
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Halder, G., Dupont, S., & Piccolo, S. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3416 · Cited by 985 · see citing works
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Dey, A., Varelas, X., & Guan, K.-L. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0070-z · Cited by 860 · see citing works
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Yimlamai, D., Christodoulou, C., Galli, G. G., Yanger, K., Pepe-Mooney, B., Gurung, B., Shrestha, K., Cahan, P., Stanger, B. Z., & Camargo, F. D. (2014) · Cell · doi:10.1016/j.cell.2014.03.060 · Cited by 857 · see citing works
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Taniguchi, K., Wu, L.-W., Grivennikov, S. I., de Jong, P. R., Lian, I., Yu, F.-X., Wang, K., Ho, S. B., Boland, B. S., Chang, J. T., et al. (2015) · Nature · doi:10.1038/nature14228 · Cited by 633 · see citing works
Self-organization and symmetry breaking in intestinal organoid development
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Zhang, W., Nandakumar, N., Shi, Y., Manzano, M., Smith, A., Graham, G., Gupta, S., Vietsch, E. E., Laughlin, S. Z., Wadhwa, M., et al. (2014) · Science Signaling · doi:10.1126/scisignal.2005049 · Cited by 360 · see citing works
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Mori, M., Triboulet, R., Mohseni, M., Schlegelmilch, K., Shrestha, K., Camargo, F. D., & Gregory, R. I. (2014) · Cell · doi:10.1016/j.cell.2013.12.043 · Cited by 335 · see citing works
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Mohseni, M., Sun, J., Lau, A., Curtis, S., Goldsmith, J., Fox, V. L., Wei, C., Frazier, M., Samson, O., Wong, K.-K., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb2884 · Cited by 294 · see citing works
Pepe-Mooney, B. J., Dill, M. T., Alemany, A., Ordovas-Montanes, J., Matsushita, Y., Rao, A., Sen, A., Miyazaki, M., Anakk, S., Dawson, P. A., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.04.004 · Cited by 266 · see citing works
Del Re, D. P., Yang, Y., Nakano, N., Cho, J., Zhai, P., Yamamoto, T., Zhang, N., Yabuta, N., Nojima, H., Pan, D., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.436311 · Cited by 249 · see citing works
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Fujii, M., Toyoda, T., Nakanishi, H., Yatabe, Y., Sato, A., Matsudaira, Y., Ito, H., Murakami, H., Kondo, Y., Kondo, E., et al. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20111653 · Cited by 224 · see citing works
Barry, E. R., & Camargo, F. D. (2013) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2012.12.006 · Cited by 214 · see citing works
Hagenbeek, T. J., Zbieg, J. R., Hafner, M., Mroue, R., Lacap, J. A., Sodir, N. M., Noland, C. L., Afghani, S., Kishore, A., Bhat, K. P., et al. (2023) · Nature Cancer · doi:10.1038/s43018-023-00577-0 · Cited by 215 · see citing works
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Xiao, L., Chen, Y., Ji, M., & Dong, J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.173468 · Cited by 190 · see citing works
Self-citationLi, L., Cui, L., Lin, P., Liu, Z., Bao, S., Ma, X., Nan, H., Zhu, W., Cen, J., Mao, Y., et al. (2023) · Cell Stem Cell · doi:10.1016/j.stem.2023.01.009 · Cited by 134 · see citing works
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Ma, X., Huang, T., Chen, X., Li, Q., Liao, M., Fu, L., Huang, J., Yuan, K., Wang, Z., & Zeng, Y. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02104-8 · Cited by 133 · see citing works
Li, W., Yang, L., He, Q., Hu, C., Zhu, L., Ma, X., Ma, X., Bao, S., Li, L., Chen, Y., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.06.008 · Cited by 124 · see citing works
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BMP4 and Gremlin 1 regulate hepatic cell senescence during clinical progression of NAFLD/NASH
Baboota, R. K., Rawshani, A., Bonnet, L., Li, X., Yang, H., Mardinoglu, A., Tchkonia, T., Kirkland, J. L., Hoffmann, A., Dietrich, A., et al. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00620-x · Cited by 99 · see citing works
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Gujral, T. S., & Kirschner, M. W. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1703096114 · Cited by 91 · see citing works
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The Hippo signal transduction network in skeletal and cardiac muscle
Wackerhage, H., Del Re, D. P., Judson, R. N., Sudol, M., & Sadoshima, J. (2014) · Science Signaling · doi:10.1126/scisignal.2005096 · Cited by 92 · see citing works
Alternative splicing rewires Hippo signaling pathway in hepatocytes to promote liver regeneration
Bangru, S., Arif, W., Seimetz, J., Bhate, A., Chen, J., Rashan, E. H., Carstens, R. P., Anakk, S., & Kalsotra, A. (2018) · Nature Structural & Molecular Biology · doi:10.1038/s41594-018-0129-2 · Cited by 85 · see citing works
Nguyen, H. B., Babcock, J. T., Wells, C. D., & Quilliam, L. A. (2013) · Oncogene · doi:10.1038/onc.2012.431 · Cited by 84 · see citing works
Macrophages harness hepatocyte glutamate to boost liver regeneration
Rigual, M. D. M., Angulo-Aguado, M., Zagorac, S., Álvarez-Díaz, R., Benítez-Mondéjar, M., Yi, F., Martínez-Garay, C., Santos-de-Frutos, K., Kim, E., Campos-Olivas, R., et al. (2025) · Nature · doi:10.1038/s41586-025-08778-6 · Cited by 53 · see citing works
Septer, S., Edwards, G., Gunewardena, S., Wolfe, A., Li, H., Daniel, J., & Apte, U. (2012) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00056.2011 · Cited by 43 · see citing works
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Meyer, K., Morales‐Navarrete, H., Seifert, S., Wilsch‐Braeuninger, M., Dahmen, U., Tanaka, E. M., Brusch, L., Kalaidzidis, Y., & Zerial, M. (2020) · Molecular Systems Biology · doi:10.15252/msb.20198985 · Cited by 39 · see citing works
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Wang, E. Y., Cheng, J.-C., Thakur, A., Yi, Y., Tsai, S.-H., & Hoodless, P. A. (2018) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2018.07.004 · Cited by 24 · see citing works
Signalling pathways and transcriptional regulators orchestrating liver development and cancer
Campbell, S. A., Stephan, T. L., Lotto, J., Cullum, R., Drissler, S., & Hoodless, P. A. (2021) · Development · doi:10.1242/dev.199814 · Cited by 22 · see citing works
Yuan, W.-C., Earl, A. S., Ma, S., Alcedo, K., Russell, J. O., Duarte, F. M., Chu, Y.-T., Chang, P.-C., Chen, H.-Y., Chi, H.-H., et al. (2025) · Cell Stem Cell · doi:10.1016/j.stem.2025.04.010 · Cited by 7 · see citing works
Expression patterns of Yes-associated protein 1 in the developing mouse liver
Wei, W., Lotto, J., & Hoodless, P. A. (2018) · Gene Expression Patterns · doi:10.1016/j.gep.2018.04.003 · Cited by 3 · see citing works
- Authors
- Zhang, N., Bai, H., David, K. K., Dong, J., Zheng, Y., Cai, J., Giovannini, M., Liu, P., Anders, R. A., & Pan, D.
- Affiliations
- Howard Hughes Medical Institute (US)
- Johns Hopkins University (US)
- House Clinic (US)
- Wellcome Sanger Institute (GB)
- Corresponding author
- Anders, Robert A.
- Pan, Duojia
- ORCID
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2010-07
- Volume
- 19
- Issue
- 1
- Pages
- 27-38
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC2925178
- OpenAlex
- W2070879574
- Cited by
- 804
- References
- 2
- Citations by year
- 2026: 21 · 2025: 34 · 2024: 57 · 2023: 44 · 2022: 81 · 2021: 61 · 2020: 58 · 2019: 56 · 2018: 61 · 2017: 57 · 2016: 45 · 2015: 68 · 2014: 50 · 2013: 35 · 2012: 42
- FWCI
- 15.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK081417)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Health Sciences › Medicine › Neurology › Neurofibromatosis and Schwannoma Cases
- Keywords
- YAP, Hippo signaling pathway, tumor suppressor, liver development, hepatocellular carcinoma, bile duct hamartoma, tissue homeostasis, organ size control, neurofibromatosis type 2, Yorkie, conditional knockout mice
- MeSH terms
- YAP-Signaling Proteins, Animals, Base Sequence, Bile Ducts, Cell Survival, Heterozygote, Homeostasis, Liver, Mice, Inbred C57BL, Mutation, Organ Size, Phenotype, Phosphoproteins, Signal Transduction, DNA Primers, Mice, Knockout, Cell Cycle Proteins, Hepatocytes, Neurofibromin 2, Adaptor Proteins, Signal Transducing, Mice
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