PAX6 Regulates Melanogenesis in the Retinal Pigmented Epithelium through Feed-Forward Regulatory Interactions with MITF

PLoS Genetics

Volumn 10, Issue 5, 2014, Pages

  Raviv, Shaul ^a   Bharti, Kapil ^b   Rencus Lazar, Sigal ^a   Cohen Tayar, Yamit ^a   Schyr, Rachel ^c   Evantal, Naveh ^c   Meshorer, Eran ^c   Zilberberg, Alona ^a   Idelson, Maria ^d   Reubinoff, Benjamin ^d   Grebe, Rhonda ^e   Rosin Arbesfeld, Rina ^a   Lauderdale, James ^f   Lutty, Gerard ^e   Arnheiter, Heinz ^g   Ashery Padan, Ruth ^a  

^a TEL AVIV UNIVERSITY   (Israel)

^b NATIONAL EYE INSTITUTE   (United States)

^c HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^d HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^e JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^f UNIVERSITY OF GEORGIA   (United States)

^g NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MICROPHTHALMIA ASSOCIATED TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR PAX6; EYE PROTEIN; HOMEODOMAIN PROTEIN; MITF PROTEIN, MOUSE; PAIRED BOX TRANSCRIPTION FACTOR; REPRESSOR PROTEIN;

ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; GENE EXPRESSION REGULATION; GENE REGULATORY NETWORK; MELANOGENESIS; MOUSE; MUTAGENESIS; NONHUMAN; PIGMENT EPITHELIUM; POSITIVE FEEDBACK; TISSUE DIFFERENTIATION; TRANSCRIPTION REGULATION; ANIMAL; BIOSYNTHESIS; CELL DIFFERENTIATION; GENETICS; GROWTH, DEVELOPMENT AND AGING; METABOLISM; ORGANOGENESIS; PIGMENTATION; PROMOTER REGION;

ANIMALS; CELL DIFFERENTIATION; EYE PROTEINS; GENE EXPRESSION REGULATION, DEVELOPMENTAL; HOMEODOMAIN PROTEINS; MICE; MICROPHTHALMIA-ASSOCIATED TRANSCRIPTION FACTOR; ORGANOGENESIS; PAIRED BOX TRANSCRIPTION FACTORS; PIGMENTATION; PROMOTER REGIONS, GENETIC; REPRESSOR PROTEINS; RETINAL PIGMENT EPITHELIUM;

EID: 84901645731     PISSN: 15537390     EISSN: 15537404     Source Type: Journal    
DOI: 10.1371/journal.pgen.1004360     Document Type: Article

References (95)

1. Strauss O, (2005) The retinal pigment epithelium in visual function. Physiol Rev 85: 845-881.
2. del Marmol V, Beermann F, (1996) Tyrosinase and related proteins in mammalian pigmentation. FEBS Lett 381: 165-168.
3. Hearing VJ, (1999) Biochemical control of melanogenesis and melanosomal organization. The journal of investigative dermatology Symposium proceedings 4: 24-28.
4. Burke JM, (2008) Epithelial phenotype and the RPE: is the answer blowing in the Wnt? Prog Retin Eye Res 27: 579-595.
5. Davis N, Yoffe C, Raviv S, Antes R, Berger J, et al. (2009) Pax6 Dosage Requirements in Iris and Ciliary Body Differentiation. Dev Biol 333: 132-42 doi: 10.1016/j.ydbio.2009.06.023.
6. Fuhrmann S, (2008) Wnt signaling in eye organogenesis. Organogenesis 4: 60-67.
7. Fuhrmann S, Levine EM, Reh TA, (2000) Extraocular mesenchyme patterns the optic vesicle during early eye development in the embryonic chick. Development 127: 4599-4609.
8. Hyer J, Mima T, Mikawa T, (1998) FGF1 patterns the optic vesicle by directing the placement of the neural retina domain. Development 125: 869-877.
9. Mochii M, Mazaki Y, Mizuno N, Hayashi H, Eguchi G, (1998) Role of Mitf in differentiation and transdifferentiation of chicken pigmented epithelial cell. Dev Biol 193: 47-62.
10. Nguyen M, Arnheiter H, (2000) Signaling and transcriptional regulation in early mammalian eye development: a link between FGF and MITF. Development 127: 3581-3591.
11. Pittack C, Grunwald GB, Reh TA, (1997) Fibroblast growth factors are necessary for neural retina but not pigmented epithelium differentiation in chick embryos. Development 124: 805-816.
12. Westenskow P, Piccolo S, 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.
13. Zhao S, Overbeek PA, (2001) Regulation of choroid development by the retinal pigment epithelium. Mol Vis 7: 277-282.
14. Bharti K, Nguyen MT, Skuntz S, Bertuzzi S, Arnheiter H, (2006) The other pigment cell: specification and development of the pigmented epithelium of the vertebrate eye. Pigment Cell Res 19: 380-394.
15. Aksan I, Goding CR, (1998) Targeting the microphthalmia basic helix-loop-helix-leucine zipper transcription factor to a subset of E-box elements in vitro and in vivo. Mol Cell Biol 18: 6930-6938.
16. Lowings P, Yavuzer U, Goding CR, (1992) Positive and negative elements regulate a melanocyte-specific promoter. Mol Cell Biol 12: 3653-3662.
17. Hemesath TJ, Steingrimsson E, McGill G, Hansen MJ, Vaught J, et al. (1994) microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family. Genes Dev 8: 2770-2780.
18. Bharti K, Liu W, Csermely T, Bertuzzi S, Arnheiter H, (2008) Alternative promoter use in eye development: the complex role and regulation of the transcription factor MITF. Development 135: 1169-1178.
19. Li XH, Kishore AH, Dao D, Zheng W, Roman CA, et al. (2010) A novel isoform of microphthalmia-associated transcription factor inhibits IL-8 gene expression in human cervical stromal cells. Mol Endocrinol 24: 1512-1528.
20. Hodgkinson CA, Moore KJ, Nakayama A, Steingrimsson E, Copeland NG, et al. (1993) Mutations at the mouse microphthalmia locus are associated with defects in a gene encoding a novel basic-helix-loop-helix-zipper protein. Cell 74: 395-404.
21. Levy C, Khaled M, Fisher DE, (2006) MITF: master regulator of melanocyte development and melanoma oncogene. Trends Mol Med 12: 406-414.
22. Takeda K, Yasumoto K, Kawaguchi N, Udono T, Watanabe K, et al. (2002) Mitf-D, a newly identified isoform, expressed in the retinal pigment epithelium and monocyte-lineage cells affected by Mitf mutations. Biochim Biophys Acta 1574: 15-23.
23. Fuse N, Yasumoto K, Takeda K, Amae S, Yoshizawa M, et al. (1999) Molecular cloning of cDNA encoding a novel microphthalmia-associated transcription factor isoform with a distinct amino-terminus. J Biochem 126: 1043-1051.
24. Takemoto CM, Yoon YJ, Fisher DE, (2002) The identification and functional characterization of a novel mast cell isoform of the microphthalmia-associated transcription factor. J Biol Chem 277: 30244-30252.
25. Udono T, Yasumoto K, Takeda K, Amae S, Watanabe K, et al. (2000) Structural organization of the human microphthalmia-associated transcription factor gene containing four alternative promoters. Biochim Biophys Acta 1491: 205-219.
26. Yajima I, Sato S, Kimura T, Yasumoto K, Shibahara S, et al. (1999) An L1 element intronic insertion in the black-eyed white (Mitf[mi-bw]) gene: the loss of a single Mitf isoform responsible for the pigmentary defect and inner ear deafness. Hum Mol Genet 8: 1431-1441.
27. Bondurand N, Pingault V, Goerich DE, Lemort N, Sock E, et al. (2000) Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome. Hum Mol Genet 9: 1907-1917.
28. Potterf SB, Furumura M, Dunn KJ, Arnheiter H, Pavan WJ, (2000) Transcription factor hierarchy in Waardenburg syndrome: regulation of MITF expression by SOX10 and PAX3. Hum Genet 107: 1-6.
29. Price ER, Horstmann MA, Wells AG, Weilbaecher KN, Takemoto CM, et al. (1998) alpha-Melanocyte-stimulating hormone signaling regulates expression of microphthalmia, a gene deficient in Waardenburg syndrome. J Biol Chem 273: 33042-33047.
30. Takeda K, Yasumoto K, Takada R, Takada S, Watanabe K, et al. (2000) Induction of melanocyte-specific microphthalmia-associated transcription factor by Wnt-3a. J Biol Chem 275: 14013-14016.
31. Watanabe A, Takeda K, Ploplis B, Tachibana M, (1998) Epistatic relationship between Waardenburg syndrome genes MITF and PAX3. Nat Genet 18: 283-286.
32. Baumer N, Marquardt T, Stoykova A, Spieler D, Treichel D, et al. (2003) Retinal pigmented epithelium determination requires the redundant activities of Pax2 and Pax6. Development 130: 2903-2915.
33. Shaham O, Menuchin Y, Farhy C, Ashery-Padan R, (2012) Pax6: a multi-level regulator of ocular development. Prog Retin Eye Res 31: 351-376.
34. Kozmik Z, (2005) Pax genes in eye development and evolution. Curr Opin Genet Dev 15: 430-438.
35. Chow RL, Altmann CR, Lang RA, Hemmati-Brivanlou A, (1999) Pax6 induces ectopic eyes in a vertebrate. Development 126: 4213-4222.
36. Davidson EH, Erwin DH, (2006) Gene regulatory networks and the evolution of animal body plans. Science 311: 796-800.
37. Bharti K, Gasper M, Ou J, Brucato M, Clore-Gronenborn K, et al. (2012) A Regulatory Loop Involving PAX6, MITF, and WNT Signaling Controls Retinal Pigment Epithelium Development. PLoS Genet 8: e1002757.
38. Drager UC, (1985) Birth dates of retinal ganglion cells giving rise to the crossed and uncrossed optic projections in the mouse. Proc R Soc Lond B Biol Sci 224: 57-77.
39. Strongin AC, Guillery RW, (1981) The distribution of melanin in the developing optic cup and stalk and its relation to cellular degeneration. J Neurosci 1: 1193-1204.
40. Ashery-Padan R, Marquardt T, Zhou X, Gruss P, (2000) Pax6 activity in the lens primordium is required for lens formation and for correct placement of a single retina in the eye. Genes Dev 14: 2701-2711.
41. Zhao S, Overbeek PA, (1999) Tyrosinase-related protein 2 promoter targets transgene expression to ocular and neural crest-derived tissues. Dev Biol 216: 154-163.
42. Chen J, Bardes EE, Aronow BJ, Jegga AG, (2009) ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res 37: W305-311.
43. Gibbs D, Azarian SM, Lillo C, Kitamoto J, Klomp AE, et al. (2004) Role of myosin VIIa and Rab27a in the motility and localization of RPE melanosomes. J Cell Sci 117: 6473-6483.
44. Cheli Y, Ohanna M, Ballotti R, Bertolotto C, (2010) Fifteen-year quest for microphthalmia-associated transcription factor target genes. Pigment Cell Melanoma Res 23: 27-40.
45. Steingrimsson E, (2010) Interpretation of complex phenotypes: lessons from the Mitf gene. Pigment Cell Melanoma Res 23: 736-740.
46. Yasumoto K, Yokoyama K, Takahashi K, Tomita Y, Shibahara S, (1997) Functional analysis of microphthalmia-associated transcription factor in pigment cell-specific transcription of the human tyrosinase family genes. J Biol Chem 272: 503-509.
47. Du J, Miller AJ, Widlund HR, Horstmann MA, Ramaswamy S, et al. (2003) MLANA/MART1 and SILV/PMEL17/GP100 are transcriptionally regulated by MITF in melanocytes and melanoma. Am J Pathol 163: 333-343.
48. Loftus SK, Antonellis A, Matera I, Renaud G, Baxter LL, et al. (2009) Gpnmb is a melanoblast-expressed, MITF-dependent gene. Pigment Cell Melanoma Res 22: 99-110.
49. Chiaverini C, Beuret L, Flori E, Busca R, Abbe P, et al. (2008) Microphthalmia-associated transcription factor regulates RAB27A gene expression and controls melanosome transport. J Biol Chem 283: 12635-12642.
50. Vetrini F, Auricchio A, Du J, Angeletti B, Fisher DE, et al. (2004) The microphthalmia transcription factor (Mitf) controls expression of the ocular albinism type 1 gene: link between melanin synthesis and melanosome biogenesis. Mol Cell Biol 24: 6550-6559.
51. Galibert MD, Yavuzer U, Dexter TJ, Goding CR, (1999) Pax3 and regulation of the melanocyte-specific tyrosinase-related protein-1 promoter. J Biol Chem 274: 26894-26900.
52. Idelson M, Alper R, Obolensky A, Ben-Shushan E, Hemo I, et al. (2009) Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells. Cell Stem Cell 5: 396-408.
53. Vugler A, Carr AJ, Lawrence J, Chen LL, Burrell K, et al. (2008) Elucidating the phenomenon of HESC-derived RPE: anatomy of cell genesis, expansion and retinal transplantation. Exp Neurol 214: 347-361.
54. Planque N, Leconte L, Coquelle FM, Martin P, Saule S, (2001) Specific Pax-6/microphthalmia transcription factor interactions involve their DNA-binding domains and inhibit transcriptional properties of both proteins. J Biol Chem 276: 29330-29337.
55. Perron M, Boy S, Amato MA, Viczian A, Koebernick K, et al. (2003) A novel function for Hedgehog signalling in retinal pigment epithelium differentiation. Development 130: 1565-1577.
56. Holme RH, Thomson SJ, Davidson DR, (2000) Ectopic expression of Msx2 in chick retinal pigmented epithelium cultures suggests a role in patterning the optic vesicle. Mech Dev 91: 175-187.
57. Fujimura N, Taketo MM, Mori M, Korinek V, 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.
58. Hallsson JH, Haflidadottir BS, Schepsky A, Arnheiter H, Steingrimsson E, (2007) Evolutionary sequence comparison of the Mitf gene reveals novel conserved domains. Pigment Cell Res 20: 185-200.
59. Bovolenta P, Mallamaci A, Briata P, Corte G, Boncinelli E, (1997) Implication of OTX2 in pigment epithelium determination and neural retina differentiation. J Neurosci 17: 4243-4252.
60. Martinez-Morales JR, Signore M, Acampora D, Simeone A, Bovolenta P, (2001) Otx genes are required for tissue specification in the developing eye. Development 128: 2019-2030.
61. Martinez-Morales JR, Dolez V, Rodrigo I, Zaccarini R, Leconte L, et al. (2003) OTX2 activates the molecular network underlying retina pigment epithelium differentiation. J Biol Chem 278: 21721-21731.
62. Takeda K, Yokoyama S, Yasumoto K, Saito H, Udono T, et al. (2003) OTX2 regulates expression of DOPAchrome tautomerase in human retinal pigment epithelium. Biochem Biophys Res Commun 300: 908-914.
63. Reinisalo M, Putula J, Mannermaa E, Urtti A, Honkakoski P, (2012) Regulation of the human tyrosinase gene in retinal pigment epithelium cells: the significance of transcription factor orthodenticle homeobox 2 and its polymorphic binding site. Mol Vis 18: 38-54.
64. Hallsson JH, Haflidadottir BS, Stivers C, Odenwald W, Arnheiter H, et al. (2004) The basic helix-loop-helix leucine zipper transcription factor Mitf is conserved in Drosophila and functions in eye development. Genetics 167: 233-241.
65. Marquardt T, Ashery-Padan R, Andrejewski N, Scardigli R, Guillemot F, et al. (2001) Pax6 is required for the multipotent state of retinal progenitor cells. Cell 105: 43-55.
66. Oron-Karni V, Farhy C, Elgart M, Marquardt T, Remizova L, et al. (2008) Dual requirement for Pax6 in retinal progenitor cells. Development 135: 4037-4047.
67. Shaham O, Smith AN, Robinson ML, Taketo MM, Lang RA, et al. (2009) Pax6 is essential for lens fiber cell differentiation. Development 136: 2567-2578.
68. Smith AN, Miller LA, Radice G, Ashery-Padan R, Lang RA, (2009) Stage-dependent modes of Pax6-Sox2 epistasis regulate lens development and eye morphogenesis. Development 136: 2977-2985.
69. Huang J, Rajagopal R, Liu Y, Dattilo LK, Shaham O, et al. (2011) The mechanism of lens placode formation: a case of matrix-mediated morphogenesis. Dev Biol 355: 32-42.
70. Grindley JC, Davidson DR, Hill RE, (1995) The role of Pax-6 in eye and nasal development. Development 121: 1433-1442.
71. Kim J, Lauderdale JD, (2006) Analysis of Pax6 expression using a BAC transgene reveals the presence of a paired-less isoform of Pax6 in the eye and olfactory bulb. Dev Biol 292: 486-505.
72. Kim J, Lauderdale JD, (2008) Overexpression of pairedless Pax6 in the retina disrupts corneal development and affects lens cell survival. Dev Biol 313: 434-454.
73. Feuda R, Hamilton SC, McInerney JO, Pisani D, (2012) Metazoan opsin evolution reveals a simple route to animal vision. Proc Natl Acad Sci U S A 109: 18868-18872.
74. Gehring WJ, Ikeo K, (1999) Pax 6: mastering eye morphogenesis and eye evolution. Trends Genet 15: 371-377.
75. Suga H, Tschopp P, Graziussi DF, Stierwald M, Schmid V, et al. (2010) Flexibly deployed Pax genes in eye development at the early evolution of animals demonstrated by studies on a hydrozoan jellyfish. Proc Natl Acad Sci U S A 107: 14263-14268.
76. Doughtie DG, Rao KR, (1984) Ultrastructure of the eyes of the grass shrimp, Palaemonetes pugio. General morphology, and light and dark adaption at noon. Cell Tissue Res 238: 271-288.
77. Davidson EH, (2011) Evolutionary bioscience as regulatory systems biology. Dev Biol 357: 35-40.
78. Yaron O, Farhy C, Marquardt T, Applebury M, Ashery-Padan R, (2006) Notch1 functions to suppress cone-photoreceptor fate specification in the developing mouse retina. Development 133: 1367-1378.
79. Baxter LL, Pavan WJ, (2003) Pmel17 expression is Mitf-dependent and reveals cranial melanoblast migration during murine development. Gene Expr Patterns 3: 703-707.
80. Baba T, Bhutto IA, Merges C, Grebe R, Emmert D, et al. (2010) A rat model for choroidal neovascularization using subretinal lipid hydroperoxide injection. Am J Pathol 176: 3085-3097.
81. Shaham O, Gueta K, Mor E, Oren-Giladi P, Grinberg D, et al. (2013) Pax6 Regulates Gene Expression in the Vertebrate Lens through miR-204. PLoS Genet 9: e1003357.
82. Levy C, Khaled M, Robinson KC, Veguilla RA, Chen PH, et al. (2010) Lineage-specific transcriptional regulation of DICER by MITF in melanocytes. Cell 141: 994-1005.
83. Sailaja BS, Takizawa T, Meshorer E, (2012) Chromatin immunoprecipitation in mouse hippocampal cells and tissues. Methods Mol Biol 809: 353-364.
84. Sailaja BS, Cohen-Carmon D, Zimmerman G, Soreq H, Meshorer E, (2012) Stress-induced epigenetic transcriptional memory of acetylcholinesterase by HDAC4. Proc Natl Acad Sci U S A 109: E3687-3695.
85. Hay-Koren A, Caspi M, Zilberberg A, Rosin-Arbesfeld R, (2011) The EDD E3 ubiquitin ligase ubiquitinates and up-regulates beta-catenin. Mol Biol Cell 22: 399-411.
86. Wolf LV, Yang Y, Wang J, Xie Q, Braunger B, et al. (2009) Identification of pax6-dependent gene regulatory networks in the mouse lens. PLoS One 4: e4159.
87. Hoashi T, Sato S, Yamaguchi Y, Passeron T, Tamaki K, et al. (2010) Glycoprotein nonmetastatic melanoma protein b, a melanocytic cell marker, is a melanosome-specific and proteolytically released protein. FASEB J 24: 1616-29.
88. Cortese K, Giordano F, Surace EM, Venturi C, Ballabio A, et al. (2005) The ocular albinism type 1 (OA1) gene controls melanosome maturation and size. Invest Ophthalmol Vis Sci 46: 4358-4364.
89. Incerti B, Cortese K, Pizzigoni A, Surace EM, Varani S, et al. (2000) Oa1 knock-out: new insights on the pathogenesis of ocular albinism type 1. Hum Mol Genet 9: 2781-2788.
90. Costin GE, Valencia JC, Vieira WD, Lamoreux ML, Hearing VJ, (2003) Tyrosinase processing and intracellular trafficking is disrupted in mouse primary melanocytes carrying the underwhite (uw) mutation. A model for oculocutaneous albinism (OCA) type 4. J Cell Sci 116: 3203-3212.
91. Du J, Fisher DE, (2002) Identification of Aim-1 as the underwhite mouse mutant and its transcriptional regulation by MITF. J Biol Chem 277: 402-406.
92. Wu XS, Rao K, Zhang H, Wang F, Sellers JR, et al. (2002) Identification of an organelle receptor for myosin-Va. Nat Cell Biol 4: 271-278.
93. Vogel P, Read RW, Vance RB, Platt KA, Troughton K, et al. (2008) Ocular albinism and hypopigmentation defects in Slc24a5-/- mice. Vet Pathol 45: 264-279.
94. Dooley TP, Curto EV, Davis RL, Grammatico P, Robinson ES, et al. (2003) DNA microarrays and likelihood ratio bioinformatic methods: discovery of human melanocyte biomarkers. Pigment Cell Res 16: 245-253.
95. Baxter LL, Pavan WJ, (2002) The oculocutaneous albinism type IV gene Matp is a new marker of pigment cell precursors during mouse embryonic development. Mech Dev 116: 209-212.