DOI QR코드

DOI QR Code

Hippo Signaling Circuit and Divergent Tissue Growth in Mammalian Eye

  • Moon, Kyeong Hwan (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Kim, Jin Woo (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST))
  • Received : 2018.03.02
  • Accepted : 2018.03.22
  • Published : 2018.04.30

Abstract

Vertebrate organ development is accompanied by demarcation of tissue compartments, which grow coordinately with their neighbors. Hence, perturbing the coordinative growth of neighboring tissue compartments frequently results in organ malformation. The growth of tissue compartments is regulated by multiple intercellular and intracellular signaling pathways, including the Hippo signaling pathway that limits the growth of various organs. In the optic neuroepithelial continuum, which is partitioned into the retina, retinal pigment epithelium (RPE) and ciliary margin (CM) during eye development, the Hippo signaling activity operates differentially, as it does in many tissues. In this review, we summarize recent studies that have explored the relationship between the Hippo signaling pathway and growth of optic neuroepithelial compartments. We will focus particularly on the roles of a tumor suppressor, neurofibromin 2 (NF2), whose expression is not only dependent on compartment-specific transcription factors, but is also subject to regulation by a Hippo-Yap feedback signaling circuit.

Keywords

References

  1. Akhmametyeva, E.M., Mihaylova, M.M., Luo, H., Kharzai, S., Welling, D.B., and Chang, L.S. (2006). Regulation of the neurofibromatosis 2 gene promoter expression during embryonic development. Dev. Dyn. 235, 2771-2785. https://doi.org/10.1002/dvdy.20883
  2. Asaoka, Y., Hata, S., Namae, M., Furutani-Seiki, M., and Nishina, H. (2014). The Hippo pathway controls a switch between retinal progenitor cell proliferation and photoreceptor cell differentiation in zebrafish. PLoS ONE 9, e97365. https://doi.org/10.1371/journal.pone.0097365
  3. Asthagiri, A.R., Parry, D.M., Butman, J.A., Kim, H.J., Tsilou, E.T., Zhuang, Z., and Lonser, R.R. (2009). Neurofibromatosis type 2. Lancet 373, 1974-1986. https://doi.org/10.1016/S0140-6736(09)60259-2
  4. Barry, E.R., Morikawa, T., Butler, B.L., Shrestha, K., de la Rosa, R., Yan, K.S., Fuchs, C.S., Magness, S.T., Smits, R., Ogino, S., et al. (2013). Restriction of intestinal stem cell expansion and the regenerative response by YAP. Nature 493, 106-110.
  5. Basu-Roy, U., Bayin, N.S., Rattanakorn, K., Han, E., Placantonakis, D.G., Mansukhani, A., and Basilico, C. (2015). Sox2 antagonizes the Hippo pathway to maintain stemness in cancer cells. Nat. Comm. 6, 6411. https://doi.org/10.1038/ncomms7411
  6. Beebe, D.C. (1986). Development of the ciliary body: a brief review. Transact. Ophthal. Soc. U. K. 105, 123-130.
  7. Belanger, M.C., Robert, B., and Cayouette, M. (2017). Msx1-Positive Progenitors in the Retinal Ciliary Margin Give Rise to Both Neural and Non-neural Progenies in Mammals. Dev. Cell 40, 137-150. https://doi.org/10.1016/j.devcel.2016.11.020
  8. Bennett, F.C., and Harvey, K.F. (2006). Fat cadherin modulates organ size in Drosophila via the Salvador/Warts/Hippo signaling pathway. Curr. Biol. 16, 2101-2110. https://doi.org/10.1016/j.cub.2006.09.045
  9. Bosch, M.M., Boltshauser, E., Harpes, P., and Landau, K. (2006a). Ophthalmologic findings and long-term course in patients with neurofibromatosis type 2. Am. J. Ophthal. 141, 1068-1077. https://doi.org/10.1016/j.ajo.2005.12.042
  10. Bosch, M.M., Wichmann, W.W., Boltshauser, E., and Landau, K. (2006b). Optic nerve sheath meningiomas in patients with neurofibromatosis type 2. Arc. Ophthal. 124, 379-385. https://doi.org/10.1001/archopht.124.3.379
  11. Bretscher, A., Edwards, K., and Fehon, R.G. (2002). ERM proteins and merlin: integrators at the cell cortex. Nat. Rev. Mol. Cell Biol. 3, 586-599.
  12. Cabochette, P., Vega-Lopez, G., Bitard, J., Parain, K., Chemouny, R., Masson, C., Borday, C., Hedderich, M., Henningfeld, K.A., Locker, M., et al. (2015). YAP controls retinal stem cell DNA replication timing and genomic stability. eLife 4, e08488.
  13. Chan, S.W., Lim, C.J., Chong, Y.F., Pobbati, A.V., Huang, C., and Hong, W. (2011). Hippo pathway-independent restriction of TAZ and YAP by angiomotin. J. Biol. Chem. 286, 7018-7026. https://doi.org/10.1074/jbc.C110.212621
  14. Chang, B., Smith, R.S., Peters, M., Savinova, O.V., Hawes, N.L., Zabaleta, A., Nusinowitz, S., Martin, J.E., Davisson, M.L., Cepko, C.L., et al. (2001). Haploinsufficient Bmp4 ocular phenotypes include anterior segment dysgenesis with elevated intraocular pressure. BMC Genet. 2, 18. https://doi.org/10.1186/1471-2156-2-18
  15. Cho, E., and Irvine, K.D. (2004). Action of fat, four-jointed, dachsous and dachs in distal-to-proximal wing signaling. Development 131, 4489-4500. https://doi.org/10.1242/dev.01315
  16. Cho, S.H., and Cepko, C.L. (2006). Wnt2b/beta-catenin-mediated canonical Wnt signaling determines the peripheral fates of the chick eye. Development 133, 3167-3177. https://doi.org/10.1242/dev.02474
  17. Chow, R.L., and Lang, R.A. (2001). Early eye development in vertebrates. Ann. Rev. Cell Dev. Biol. 17, 255-296. https://doi.org/10.1146/annurev.cellbio.17.1.255
  18. Christ, A., Christa, A., Klippert, J., Eule, J.C., Bachmann, S., Wallace, V.A., Hammes, A., and Willnow, T.E. (2015). LRP2 acts as SHH clearance receptor to protect the retinal margin from mitogenic stimuli. Dev. Cell 35, 36-48. https://doi.org/10.1016/j.devcel.2015.09.001
  19. Cicero, S.A., Johnson, D., Reyntjens, S., Frase, S., Connell, S., Chow, L.M., Baker, S.J., Sorrentino, B.P., and Dyer, M.A. (2009). Cells previously identified as retinal stem cells are pigmented ciliary epithelial cells. Proc. Natl. Acad. Sci. U SA 106, 6685-6690. https://doi.org/10.1073/pnas.0901596106
  20. Curto, M., Cole, B.K., Lallemand, D., Liu, C.-H., and McClatchey, A.I. (2007). Contact-dependent inhibition of EGFR signaling by Nf2/Merlin. J. Cell Biol. 177, 893-903. https://doi.org/10.1083/jcb.200703010
  21. Curto, M., and McClatchey, A.I. (2007). Nf2/Merlin: a coordinator of receptor signalling and intercellular contact. Br. J. Cancer 98, 256-262.
  22. Fuhrmann, S., Riesenberg, A.N., Mathiesen, A.M., Brown, E.C., Vetter, M.L., and Brown, N.L. (2009). Characterization of a transient TCF/LEF-responsive progenitor population in the embryonic mouse retina. Invest. Ophthal. Vis. Sci. 50, 432-440. https://doi.org/10.1167/iovs.08-2270
  23. Fuhrmann, S., Zou, C., and Levine, E.M. (2014). Retinal pigment epithelium development, plasticity, and tissue homeostasis. Exp. Eye Res. 123, 141-150. https://doi.org/10.1016/j.exer.2013.09.003
  24. Fujimura, N., Taketo, M.M., Mori, M., Korinek, V., and Kozmik, Z. (2009). Spatial and temporal regulation of Wnt/${\beta}$-catenin signaling is essential for development of the retinal pigment epithelium. Dev. Biol. 334, 31-45. https://doi.org/10.1016/j.ydbio.2009.07.002
  25. Graw, J. (2010). Eye development. Curr. Top. Dev. Biol. 90, 343-386.
  26. Grzeschik, N.A., Parsons, L.M., Allott, M.L., Harvey, K.F., and Richardson, H.E. (2010). Lgl, aPKC, and Crumbs regulate the Salvador/Warts/Hippo pathway through two distinct mechanisms. Curr. Biol. 20, 573-581. https://doi.org/10.1016/j.cub.2010.01.055
  27. Ha, T., Moon, K.H., Dai, L., Hatakeyama, J., Yoon, K., Park, H.S., Kong, Y.Y., Shimamura, K., and Kim, J.W. (2017). The Retinal Pigment Epithelium Is a Notch Signaling Niche in the Mouse Retina. Cell Rep. 19, 351-363. https://doi.org/10.1016/j.celrep.2017.03.040
  28. Hamaratoglu, F., Willecke, M., Kango-Singh, M., Nolo, R., Hyun, E., Tao, C., Jafar-Nejad, H., and Halder, G. (2006). The tumoursuppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis. Nat. Cell Biol. 8, 27-36. https://doi.org/10.1038/ncb1339
  29. Harvey, K.F., Pfleger, C.M., and Hariharan, I.K. (2003). The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis. Cell 114, 457-467. https://doi.org/10.1016/S0092-8674(03)00557-9
  30. Huang, J., Wu, S., Barrera, J., Matthews, K., and Pan, D. (2005). The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP. Cell 122, 421-434. https://doi.org/10.1016/j.cell.2005.06.007
  31. Huang, J.M., Nagatomo, I., Suzuki, E., Mizuno, T., Kumagai, T., Berezov, A., Zhang, H., Karlan, B., Greene, M.I., and Wang, Q. (2013). YAP modifies cancer cell sensitivity to EGFR and survivin inhibitors and is negatively regulated by the non-receptor type protein tyrosine phosphatase 14. Oncogene 32, 2220-2229. https://doi.org/10.1038/onc.2012.231
  32. Kanai, F., Marignani, P.A., Sarbassova, D., Yagi, R., Hall, R.A., Donowitz, M., Hisaminato, A., Fujiwara, T., Ito, Y., Cantley, L.C., et al. (2000). TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins. EMBO J. 19, 6778-6791. https://doi.org/10.1093/emboj/19.24.6778
  33. Kim, H.T., and Kim, J.W. (2012). Compartmentalization of vertebrate optic neuroephithelium: external cues and transcription factors. Mol. Cells 33, 317-324. https://doi.org/10.1007/s10059-012-0030-5
  34. Kim, J.Y., Park, R., Lee, J.H., Shin, J., Nickas, J., Kim, S., and Cho, S.H. (2016). Yap is essential for retinal progenitor cell cycle progression and RPE cell fate acquisition in the developing mouse eye. Dev. Biol. 419, 336-347. https://doi.org/10.1016/j.ydbio.2016.09.001
  35. Kim, N.G., Koh, E., Chen, X., and Gumbiner, B.M. (2011). E-cadherin mediates contact inhibition of proliferation through Hippo signalingpathway components. P Proc. Natl. Acad. Sci. USA 108, 11930-11935. https://doi.org/10.1073/pnas.1103345108
  36. Lai, Z.C., Wei, X., Shimizu, T., Ramos, E., Rohrbaugh, M., Nikolaidis, N., Ho, L.L., and Li, Y. (2005). Control of cell proliferation and apoptosis by mob as tumor suppressor, mats. Cell 120, 675-685. https://doi.org/10.1016/j.cell.2004.12.036
  37. Landau, K., and Yasargil, G.M. (1993). Ocular fundus in neurofibromatosis type 2. Br. J. Ophthal. 77, 646-649. https://doi.org/10.1136/bjo.77.10.646
  38. Lavado, A., He, Y., Pare, J., Neale, G., Olson, E.N., Giovannini, M., and Cao, X. (2013). Tumor suppressor Nf2 limits expansion of the neural progenitor pool by inhibiting Yap/Taz transcriptional coactivators. Development 140, 3323-3334. https://doi.org/10.1242/dev.096537
  39. Li, W., You, L., Cooper, J., Schiavon, G., Pepe-Caprio, A., Zhou, L., Ishii, R., Giovannini, M., Hanemann, C.O., Long, S.B., et al. (2010). Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus. Cell 140, 477-490. https://doi.org/10.1016/j.cell.2010.01.029
  40. Li, W., Cooper, J., Karajannis, M.A., and Giancotti, F.G. (2012). Merlin: a tumour suppressor with functions at the cell cortex and in the nucleus. EMBO Rep. 13, 204-215. https://doi.org/10.1038/embor.2012.11
  41. Li, Y., Zhou, H., Li, F., Chan, S.W., Lin, Z., Wei, Z., Yang, Z., Guo, F., Lim, C.J., Xing, W., et al. (2015). Angiomotin binding-induced activation of Merlin/NF2 in the Hippo pathway. Cell Res. 25, 801-817. https://doi.org/10.1038/cr.2015.69
  42. Lian, I., Kim, J., Okazawa, H., Zhao, J., Zhao, B., Yu, J., Chinnaiyan, A., Israel, M.A., Goldstein, L.S., Abujarour, R., et al. (2010). The role of YAP transcription coactivator in regulating stem cell self-renewal and differentiation. Genes Dev. 24, 1106-1118. https://doi.org/10.1101/gad.1903310
  43. Liu, H., Mohamed, O., Dufort, D., and Wallace, V.A. (2003). Characterization of Wnt signaling components and activation of the Wnt canonical pathway in the murine retina. Dev. Dyn. 227, 323-334. https://doi.org/10.1002/dvdy.10315
  44. Liu, H., Xu, S., Wang, Y., Mazerolle, C., Thurig, S., Coles, B.L.K., Ren, J.C., Taketo, M.M., van der Kooy, D., and Wallace, V.A. (2007). Ciliary margin transdifferentiation from neural retina is controlled by canonical Wnt signaling. Dev. Biol. 308, 54-67. https://doi.org/10.1016/j.ydbio.2007.04.052
  45. Liu, X., Yang, N., Figel, S.A., Wilson, K.E., Morrison, C.D., Gelman, I.H., and Zhang, J. (2013). PTPN14 interacts with and negatively regulates the oncogenic function of YAP. Oncogene 32, 1266-1273. https://doi.org/10.1038/onc.2012.147
  46. Marcucci, F., Murcia-Belmonte, V., Coca, Y., Ferreiro-Galve, S., Wang, Q., Kuwajima, T., Khalid, S., Ross, M.E., Herrera, E., and Mason, C. (2016). The ciliary margin zone of the mammalian retina generates retinal ganglion cells. Cell Rep. 17, 3153-3164. https://doi.org/10.1016/j.celrep.2016.11.016
  47. McLaughlin, M.E., Pepin, S.M., Maccollin, M., Choopong, P., and Lessell, S. (2007). Ocular pathologic findings of neurofibromatosis type 2. Arc. Ophthal. 125, 389-394. https://doi.org/10.1001/archopht.125.3.389
  48. Miesfeld, J.B., Gestri, G., Clark, B.S., Flinn, M.A., Poole, R.J., Bader, J.R., Besharse, J.C., Wilson, S.W., and Link, B.A. (2015). Yap and Taz regulate retinal pigment epithelial cell fate. Development 142, 3021-3032. https://doi.org/10.1242/dev.119008
  49. 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). A genetic screen identifies an LKB1-MARK signalling axis controlling the Hippo-YAP pathway. Nat. Cell Biol. 16, 108-117. https://doi.org/10.1038/ncb2884
  50. Mononen, T.K., K.; Tuppurainen, K. (2007). Colobomatous microphthalmia and a cyst associated with a nonsense NF2 gene mutation. Am. Genet. Soc. f20750.
  51. Moon, K.H., Kim, H.T., Lee, D., Rao, M.B., Levine, E.M., Lim, D.S., and Kim, J.W. (2018). Differential Expression of NF2 in Neuroepithelial Compartments Is Necessary for Mammalian Eye Development. Dev. Cell 44, 13-28 e13. https://doi.org/10.1016/j.devcel.2017.11.011
  52. Moroishi, T., Park, H.W., Qin, B., Chen, Q., Meng, Z., Plouffe, S.W., Taniguchi, K., Yu, F.X., Karin, M., Pan, D., et al. (2015). A YAP/TAZ induced feedback mechanism regulates Hippo pathway homeostasis. Genes Dev. 29, 1271-1284. https://doi.org/10.1101/gad.262816.115
  53. Napier, H.R.L., and Kidson, S.H. (2005). Proliferation and cell shape changes during ciliary body morphogenesis in the mouse. Dev. Dyn. 233, 213-223. https://doi.org/10.1002/dvdy.20302
  54. Ohgushi, M., Minaguchi, M., and Sasai, Y. (2015). Rho-Signaling-Directed YAP/TAZ Activity Underlies the Long-Term Survival and Expansion of Human Embryonic Stem Cells. Cell Stem Cell 17, 448-461. https://doi.org/10.1016/j.stem.2015.07.009
  55. Ohta, K., Ito, A., and Tanaka, H. (2008). Neuronal stem/progenitor cells in the vertebrate eye. Dev. Growth Diff. 50, 253-259. https://doi.org/10.1111/j.1440-169X.2008.01006.x
  56. Robinson, B.S., Huang, J., Hong, Y., and Moberg, K.H. (2010). Crumbs regulates Salvador/Warts/Hippo signaling in Drosophila via the FERM-domain protein Expanded. Curr. Biol. 20, 582-590. https://doi.org/10.1016/j.cub.2010.03.019
  57. Schlegelmilch, K., Mohseni, M., Kirak, O., Pruszak, J., Rodriguez, J.R., Zhou, D., Kreger, B.T., Vasioukhin, V., Avruch, J., Brummelkamp, T.R., et al. (2011). Yap1 acts downstream of alpha-catenin to control epidermal proliferation. Cell 144, 782-795. https://doi.org/10.1016/j.cell.2011.02.031
  58. Serinagaoglu, Y., Pare, J., Giovannini, M., and Cao, X. (2015). Nf2-Yap signaling controls the expansion of DRG progenitors and glia during DRG development. Dev. Biol. 398, 97-109. https://doi.org/10.1016/j.ydbio.2014.11.017
  59. Sivalingam, A., Augsburger, J., Perilongo, G., Zimmerman, R., and Barabas, G. (1991). Combined hamartoma of the retina and retinal pigment epithelium in a patient with neurofibromatosis type 2. J. Ped. Ophthal. Strabis. 28, 320-322.
  60. Song, J.Y., Park, R., Kim, J.Y., Hughes, L., Lu, L., Kim, S., Johnson, R.L., and Cho, S.H. (2014). Dual function of Yap in the regulation of lens progenitor cells and cellular polarity. Dev. Biol. 386, 281-290. https://doi.org/10.1016/j.ydbio.2013.12.037
  61. St John, M.A., Tao, W., Fei, X., Fukumoto, R., Carcangiu, M.L., Brownstein, D.G., Parlow, A.F., McGrath, J., and Xu, T. (1999). Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction. Nat. Genet. 21, 182-186. https://doi.org/10.1038/5965
  62. Stanger, B.Z. (2008). Organ size determination and the limits of regulation. Cell Cycle 7, 318-324. https://doi.org/10.4161/cc.7.3.5348
  63. Sudol, M. (1994). Yes-associated protein (YAP65) is a proline-rich phosphoprotein that binds to the SH3 domain of the Yes protooncogene product. Oncogene 9, 2145-2152.
  64. Tapon, N., Harvey, K.F., Bell, D.W., Wahrer, D.C., Schiripo, T.A., Haber, D., and Hariharan, I.K. (2002). salvador Promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines. Cell 110, 467-478. https://doi.org/10.1016/S0092-8674(02)00824-3
  65. Tropepe, V., Coles, B.L., Chiasson, B.J., Horsford, D.J., Elia, A.J., McInnes, R.R., and van der Kooy, D. (2000). Retinal stem cells in the adult mammalian eye. Science 287, 2032-2036. https://doi.org/10.1126/science.287.5460.2032
  66. Udan, R.S., Kango-Singh, M., Nolo, R., Tao, C., and Halder, G. (2003). Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathway. Nat. Cell Biol. 5, 914-920. https://doi.org/10.1038/ncb1050
  67. Verghese, S., Waghmare, I., Kwon, H., Hanes, K., and Kango-Singh, M. (2012). Scribble acts in the Drosophila fat-hippo pathway to regulate warts activity. PLoS ONE 7, e47173. https://doi.org/10.1371/journal.pone.0047173
  68. Wang, Y., Dakubo, G.D., Thurig, S., Mazerolle, C.J., and Wallace, V.A. (2005). Retinal ganglion cell-derived sonic hedgehog locally controls proliferation and the timing of RGC development in the embryonic mouse retina. Development 132, 5103-5113. https://doi.org/10.1242/dev.02096
  69. Westenskow, P., Piccolo, S., and Fuhrmann, S. (2009). Beta-catenin controls differentiation of the retinal pigment epithelium in the mouse optic cup by regulating Mitf and Otx2 expression. Development 136, 2505-2510. https://doi.org/10.1242/dev.032136
  70. Wiley, L.A., Dattilo, L.K., Kang, K.B., Giovannini, M., and Beebe, D.C. (2010). The Tumor Suppressor Merlin Is Required for Cell Cycle Exit, Terminal Differentiation, and Cell Polarity in the Developing Murine Lens. Invest. Ophthal. Vis. Sci. 51, 3611-3618. https://doi.org/10.1167/iovs.09-4371
  71. Wu, S., Huang, J., Dong, J., and Pan, D. (2003). hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts. Cell 114, 445-456. https://doi.org/10.1016/S0092-8674(03)00549-X
  72. Yu, F.X., and Guan, K.L. (2013). The Hippo pathway: regulators and regulations. Genes Dev. 27, 355-371. https://doi.org/10.1101/gad.210773.112
  73. Yue, T., Tian, A., and Jiang, J. (2012). The cell adhesion molecule echinoid functions as a tumor suppressor and upstream regulator of the Hippo signaling pathway. Dev. Cell 22, 255-267. https://doi.org/10.1016/j.devcel.2011.12.011
  74. Zhang, N., Bai, H., David, K.K., Dong, J., Zheng, Y., Cai, J., Giovannini, M., Liu, P., Anders, R.A., and Pan, D. (2010). The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals. Dev. Cell 19, 27-38. https://doi.org/10.1016/j.devcel.2010.06.015
  75. Zhang, H., Deo, M., Thompson, R.C., Uhler, M.D., and Turner, D.L. (2012). Negative regulation of Yap during neuronal differentiation. Dev. Biol. 361, 103-115. https://doi.org/10.1016/j.ydbio.2011.10.017
  76. Zhao, S., Chen, Q., Hung, F.C., and Overbeek, P.A. (2002). BMP signaling is required for development of the ciliary body. Development 129, 4435-4442.
  77. Zhou, Y., Tanzie, C., Yan, Z., Chen, S., Duncan, M., Gaudenz, K., Li, H., Seidel, C., Lewis, B., Moran, A., et al. (2013). Notch2 regulates BMP signaling and epithelial morphogenesis in the ciliary body of the mouse eye. Proc. Natl. Acad. Sci. USA 110, 8966-8971. https://doi.org/10.1073/pnas.1218145110

Cited by

  1. Yap haploinsufficiency leads to Müller cell dysfunction and late-onset cone dystrophy vol.11, pp.8, 2018, https://doi.org/10.1038/s41419-020-02860-9
  2. Nf2 fine-tunes proliferation and tissue alignment during closure of the optic fissure in the embryonic mouse eye vol.29, pp.20, 2018, https://doi.org/10.1093/hmg/ddaa228
  3. The Short-Chain Fatty Acid Receptor GPR43 Modulates YAP/TAZ via RhoA vol.44, pp.7, 2021, https://doi.org/10.14348/molcells.2021.0021