Wnt signaling in skin development, homeostasis, and disease

Cold Spring Harbor Perspectives in Biology

Volumn 5, Issue 2, 2013, Pages

  Lim, Xinhong ^a   Nusse, Roel ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; CELL LINEAGE; EPITHELIZATION; GROWTH, DEVELOPMENT AND AGING; HAIR DISEASE; HAIR FOLLICLE; HOMEOSTASIS; MELANOCYTE; METABOLISM; SKIN; SKIN DISEASE; WNT SIGNALING PATHWAY;

CELL LINEAGE; HAIR DISEASES; HAIR FOLLICLE; HOMEOSTASIS; MELANOCYTES; RE-EPITHELIALIZATION; SKIN; SKIN DISEASES; WNT SIGNALING PATHWAY;

EID: 84875153351     PISSN: None     EISSN: 19430264     Source Type: Journal    
DOI: 10.1101/cshperspect.a008029     Document Type: Article

References (126)

1. Adaimy L, Chouery E, Megarbane H, Mroueh S, Delague V, Nicolas E, Belguith H, de Mazancourt P, Megarbane A. 2007. Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia: The odonto-onycho-dermal dysplasia. Am J Hum Genet 81: 821-828.
2. Ambler CA, Määttä A. 2009. Epidermal stem cells: Location, potential and contribution to cancer. J Pathol 217: 206-216.
3. Andl T, Reddy ST, Gaddapara T, Millar SE. 2002. WNT signals are required for the initiation of hair follicle development. Dev Cell 2: 643-653.
4. Andl T, Ahn K, Kairo A, Chu EY, Wine-Lee L, Reddy ST, Croft NJ, Cebra-Thomas JA, Metzger D, Chambon P, et al. 2004. Epithelial Bmpr1a regulates differentiation and proliferation in postnatal hair follicles and is essential for tooth development. Development 131: 2257-2268.
5. Atit R, Sgaier SK, Mohamed OA, Taketo MM, Dufort D, Joyner AL, Niswander L, Conlon RA. 2006. b-Catenin activation is necessary and sufficient to specify the dorsal dermal fate in the mouse. Dev Biol 296: 164-176.
6. Bachmann IM, Straume O, Puntervoll HE, Kalvenes MB, Akslen LA. 2005. Importance of P-cadherin, b-catenin, and Wnt5a/frizzled for progression of melanocytic tumors and prognosis incutaneous melanoma. Clin Cancer Res 11: 8606-8614.
7. Barrott JJ, Cash GM, Smith AP, Barrow JR, Murtaugh LC. 2011. Deletion of mouse Porcn blocks Wnt ligand secretion and reveals an ectodermal etiology of human focal dermal hypoplasia/Goltz syndrome. Proc Natl Acad Sci 108: 12752-12757.
8. Bhowmick NA, Neilson EG, Moses HL. 2004. Stromal fibroblasts in cancer initiation and progression. Nature 432: 332-337.
9. Biechele TL, Kulikauskas RM, Toroni RA, Lucero OM, Swift RD, James RG, Robin NC, Dawson DW, Moon RT, Chien AJ. 2012. Wnt/b-catenin signaling and AXIN1 regulate apoptosis triggered by inhibition of the mutant Kinase BRAFV600E in human melanoma. Sci Signal 5: ra3.
10. Blanpain C, Fuchs E. 2006. Epidermal stem cells of the skin. Annu Rev Cell Dev Biol 22: 339-373.
11. Blanpain C, Fuchs E. 2009. Epidermal homeostasis: A balancing act of stem cells in the skin. Nat Rev Mol Cell Biol 10: 207-217.
12. Blanpain C, Lowry WE, Geoghegan A, Polak L, Fuchs E. 2004. Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell 118: 635-648.
13. Bohring A, Stamm T, Spaich C, Haase C, Spree K, Hehr U, Hoffmann M, Ledig S, Sel S, Wieacker P, et al. 2009. WNT10A mutations are afrequent cause of a broad spectrum of ectodermal dysplasias with sex-biased manifestation pattern in heterozygotes. Am J Hum Genet 85: 97-105.
14. Botchkarev VA, Botchkareva NV, Nakamura M, Huber O, Funa K, Lauster R, Paus R, Gilchrest BA. 2001. Noggin is required for induction of the hair follicle growth phase in postnatal skin. FASEB J 15: 2205-2214.
15. Castilho RM, Squarize CH, Chodosh LA, Williams BO, Gutkind JS. 2009. mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging. Cell Stem Cell 5:279-289.
16. Chan EF, Gat U, McNiff JM, Fuchs E. 1999. A common human skin tumour is caused by activating mutations in b-catenin. Nat Genet 21: 410-413.
17. Chanda S, Robinette CL, Couse JF, Smart RC. 2000. 17bEstradiol and ICI-182780 regulate the hair follicle cycle in mice through an estrogen receptor-a pathway. Am J Physiol Endocrinol Metab 278: E202-E210.
18. Chien AJ, Moore EC, Lonsdorf AS, Kulikauskas RM, Rothberg BG, Berger AJ, Major MB, Hwang ST, Rimm DL, Moon RT. 2009. Activated Wnt/b-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and amurine melanoma model. Proc Natl Acad Sci 106: 1193-1198.
19. Cotsarelis G, Sun T-T, Lavker RM. 1990. Label-retaining cells reside in the bulge area of pilosebaceous unit: Implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell 61: 1329-1337.
20. DasGupta R, Fuchs E. 1999. Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation. Development 126: 4557-4568.
21. DasGupta R, Rhee H, Fuchs E. 2002. A developmental conundrum: A stabilized form of b-catenin lacking the transcriptional activation domain triggers features of hair cell fate in epidermal cells and epidermal cell fate in hair follicle cells. J Cell Biol 158: 331-344.
22. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, et al. 2002. Mutations of the BRAF gene in human cancer. Nature 417: 949-954.
23. Delmas V, Beermann F, Martinozzi S, Carreira S, Ackermann J, Kumasaka M, Denat L, Goodall J, Luciani F, Viros A, et al. 2007. b-catenin induces immortalization of melanocytes by suppressing p16INK4a expression and cooperates with N-Ras in melanoma development. Genes Dev 21: 2923-2935.
24. Devenport D, Fuchs E. 2008. Planar polarization in embryonic epidermis orchestrates global asymmetric morphogenesis of hair follicles. Nat Cell Biol 10: 1257-1268.
25. Devenport D, Oristian D, Heller E, Fuchs E. 2011. Mitotic internalization of planar cell polarity proteins preserves tissue polarity. Nat Cell Biol 13: 893-902.
26. Dorsky RI, Moon RT, Raible DW. 1998. Control of neural crest cell fate by the Wnt signalling pathway. Nature 396: 370-373.
27. Dorsky RI, Raible DW, Moon RT. 2000. Direct regulation of nacre, a zebrafish MITF homolog required for pigment cell formation, by the Wnt pathway. Genes Dev 14: 158-162.
28. Dunn KJ, Williams BO, Li Y, Pavan WJ. 2000. Neural crestdirected gene transfer demonstrates Wnt1 role in melanocyte expansion and differentiation during mouse development. Proc Natl Acad Sci 97: 10050-10055.
29. Enshell-Seijffers D, Lindon C, Kashiwagi M, Morgan BA. 2010. b-catenin activity in the dermal papilla regulates morphogenesis and regeneration of hair. Dev Cell 18: 633-642.
30. Estrach S, Ambler CA, Lo Celso C, Hozumi K, Watt FM. 2006. Jagged 1 is a b-catenin target gene required for ectopic hair follicle formation in adult epidermis. Development 133: 4427-4438.
31. Fuchs E. 2007. Scratching the surface of skin development. Nature 445: 834.
32. Fuchs E, Horsley V. 2008. More than one way to skin. Genes Dev 22: 976-985.
33. Gat U, DasGupta R, Degenstein L, Fuchs E. 1998. De Novo hair follicle morphogenesis and hair tumors in mice expressing a truncated b-catenin in skin. Cell 95: 605-614.
34. Greco V, Chen T, Rendl M, Schober M, Pasolli HA, Stokes N, Cruz-Racelis Dela J, Fuchs E. 2009. A two-step mechanism for stem cell activation during hair regeneration. Cell Stem Cell 4: 155-169.
35. Hardy MH. 1992. The secret life of the hair follicle. Trends Genet 8: 55-61.
36. Hsu Y-C, Pasolli HA, Fuchs E. 2011. Dynamics between stem cells, niche, and progeny in the hair follicle. Cell 144: 92-105.
37. Hu B, Lefort K, Qiu W, Nguyen BC, Rajaram RD, Castillo E, He F, Chen Y, Angel P, Brisken C, et al. 2010. Control of hair follicle cell fate by underlying mesenchyme through a CSL-Wnt5a-FoxN1 regulatory axis. Genes Dev 24: 1519-1532.
38. Huelsken J, Vogel R, Erdmann B, Cotsarelis G, Birchmeier W. 2001. b-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell 105: 533-545.
39. Ikeya M, Lee SM, Johnson JE, McMahon AP, Takada S. 1997. Wnt signalling required for expansion of neural crest and CNS progenitors. Nature 389: 966-970.
40. Ito M, Yang Z, Andl T, Cui C, Kim N, Millar SE, Cotsarelis G. 2007. Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding. Nature 447: 316-320.
41. Jaks V, Barker N, Kasper M, van Es JH, Snippert HJ, Clevers H, Toftgård R. 2008. Lgr5 marks cycling, yet long-lived, hair follicle stem cells. Nat Genet 40: 1291-1299.
42. Jiang T-X, Widelitz RB, Shen W-M, Will P, Wu D-Y, Lin CM, Jung H-S, Chuong C-M. 2004. Integument pattern formation involves genetic and epigenetic controls: Feather arrays simulated by digital hormone models. Int J Dev Biol 48: 117-135.
43. Kageshita T, Hamby CV, Ishihara T, Matsumoto K, Saida T, Ono T. 2001. Loss of b-catenin expression associated with disease progression in malignant melanoma. Br J Dermatol 145: 210-216.
44. Kalluri R, Zeisberg M. 2006. Fibroblasts in cancer. Nat Rev Cancer 6: 392-401.
45. Klaus A, Birchmeier W. 2008. Wnt signalling and its impact on development and cancer. Nat Rev Cancer 8: 387-398.
46. Kobielak K, Pasolli HA, Alonso L, Polak L, Fuchs E. 2003. Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA. J Cell Biol 163: 609-623.
47. Kobielak K, Stokes N, la Cruz de J, Polak L, Fuchs E. 2007. Loss of a quiescent niche but not follicle stem cells in the absence of bone morphogenetic protein signaling. Proc Natl Acad Sci 104: 10063-10068.
48. Kratochwil K, Dull M, Farinas I, Galceran J, Grosschedl R. 1996. Lef1 expressionis activated by BMP-4 and regulates inductive tissue interactions in tooth and hair development. Genes Dev 10: 1382-1394.
49. Lang D, Lu M-M, Huang L, Engleka KA, Zhang M, Chu EY, Lipner S, Skoultchi A, Millar SE, Epstein JA. 2005. Pax3 functions at a nodal point in melanocyte stem cell differentiation. Nature 433: 884-887.
50. Levy V, Lindon C, Harfe BD, Morgan BA. 2005. Distinct stem cell populations regenerate the follicle and interfollicular epidermis. Dev Cell 9: 855-861.
51. Lien W-H, Guo X, Polak L, Lawton LN, Young RA, Zheng D, Fuchs E. 2011. Genome-wide maps of histone modifications unwind in vivo chromatin states of the hair follicle lineage. Cell Stem Cell 9: 219-232.
52. Lo Celso C, Prowse DM, Watt FM. 2004. Transient activation of b-catenin signalling in adult mouse epidermis is sufficient to induce new hair follicles but continuous activation is required to maintain hair follicle tumours. Development 131: 1787-1799.
53. Lo Celso C, Berta MA, Braun KM, Frye M, Lyle S, Zouboulis CC, Watt FM. 2008. Characterization of bipotential epidermal progenitors derived from human sebaceous gland: Contrasting roles of c-Myc and b-catenin. Stem Cells 26: 1241-1252.
54. Lowry WE, Blanpain C, Nowak JA, Guasch G, Lewis L, Fuchs E. 2005. Defining the impact of b-catenin/Tcf transactivation on epithelial stem cells. Genes Dev 19: 1596-1611.
55. Maelandsmo GM, Holm R, Nesland JM, Fodstad Ø, Flørenes VA. 2003. Reduced b-catenin expression in the cytoplasm of advanced-stage superficial spreading malignant melanoma. Clin Cancer Res 9: 3383-3388.
56. Maini PK, Baker RE, Chuong C-M. 2006. Developmental biology. The Turing model comes of molecular age. Science 314: 1397-1398.
57. Malanchi I, Peinado H, Kassen D, Hussenet T, Metzger D, Chambon P, Huber M, Hohl D, Cano A, Birchmeier W, et al. 2008. Cutaneous cancer stem cell maintenance is dependent on b-catenin signalling. Nature 452: 650- 653.
58. Merrill BJ, Gat U, DasGupta R, Fuchs E. 2001. Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin. Genes Dev 15: 1688-1705.
59. Millar SE. 2002. Molecular mechanisms regulating hair follicle development. J Invest Dermatol 118: 216.
60. Millar SE, Willert K, Salinas PC, Roelink H, Nusse R, Sussman DJ, Barsh GS. 1999. WNTsignaling in the control of hair growth and structure. Dev Biol 207: 133-149.
61. Morelli LG, Uriu K, Ares S, Oates AC. 2012. Computational approaches to developmental patterning. Science 336: 187-191.
62. Morris RJ, Liu Y, Marles L, Yang Z, Trempus C, Li S, Lin JS, Sawicki JA, Cotsarelis G. 2004. Capturing and profiling adult hair follicle stem cells. Nat Biotechnol 22: 411-417.
63. Müller-Röver S, Handjiski B, van der Veen C, Eichmüller S, Foitzik K, McKay IA, Stenn KS, Paus R. 2001. A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages. J Invest Dermatol 117: 3-15.
64. Närhi K, Järvinen E, Birchmeier W, Taketo MM, Mikkola ML, Thesleff I. 2008. Sustained epithelial b-catenin activity induces precocious hair development but disrupts hair follicle down-growth and hair shaft formation. Development 135: 1019-1028.
65. Nawaz S, Klar J, Wajid M, Aslam M, Tariq M, Schuster J, Baig SM, Dahl N. 2009. WNT10A missense mutation associated with a complete Odonto-Onycho-Dermal Dysplasia syndrome. Eur J Hum Genet 17: 1600-1605.
66. Nguyen H, Rendl M, Fuchs E. 2006. Tcf3 governs stem cell features and represses cell fate determination in skin. Cell 127: 171-183.
67. Nguyen H, Merrill BJ, Polak L, Nikolova M, Rendl M, Shaver TM, Pasolli HA, Fuchs E. 2009. Tcf3 and Tcf4 are essential for long-term homeostasis of skin epithelia. Nat Genet 41: 1068-1075.
68. Niemann C, Watt FM. 2002. Designer skin: Lineage commitment inpostnatal epidermis. Trends Cell Biol 12: 185-192.
69. Niemann C, Owens DM, Hülsken J, Birchmeier W, Watt FM. 2002. Expression of DNLef1 in mouse epidermis results in differentiation of hair follicles into squamous epidermal cysts and formation of skin tumours. Development 129: 95-109.
70. Niemann C, Owens DM, Schettina P, Watt FM. 2007. Dual role of inactivating Lef1 mutations in epidermis: Tumor promotion and specification of tumor type. Cancer Res 67: 2916-2921.
71. Nishimura EK, Jordan SA, Oshima H, Yoshida H, Osawa M, Moriyama M, Jackson IJ, Barrandon Y, Miyachi Y, Nishikawa S-I. 2002. Dominant roleof the niche inmelanocyte stem-cell fate determination. Nature 416: 854-860.
72. Nishimura EK, Suzuki M, Igras V, Du J, Lonning S, Miyachi Y, Roes J, Beermann F, Fisher DE. 2010. Key roles for transforming growth factor b in melanocyte stem cell maintenance. Cell Stem Cell 6: 130-140.
73. Noramly S, Freeman A, Morgan BA. 1999. b-catenin signaling can initiate feather bud development. Development 126: 3509-3521.
74. Ohtola J, Myers J, Akhtar-Zaidi B, Zuzindlak D, Sandesara P, Yeh K, Mackem S, Atit R. 2008. b-catenin has sequential roles in the survival and specification of ventral dermis. Development 135: 2321-2329.
75. Ohyama M, Terunuma A, Tock CL, Radonovich MF, PiseMasison CA, Hopping SB, Brady JN, Udey MC, Vogel JC. 2006. Characterization and isolation of stem cell-enriched human hair follicle bulge cells. J Clin Invest 116: 249-260.
76. Oliver RF, Jahoda CA. 1988. Dermal-epidermal interactions. Clin Dermatol 6: 74-82.
77. Olivera-Martinez I, Thélu J, Teillet MA, Dhouailly D. 2001. Dorsal dermis development depends on a signal from the dorsal neural tube, which can be substituted by Wnt-1. Mech Dev 100: 233-244.
78. Oshimori N, Fuchs E. 2012. Paracrine TGF-b signaling counterbalances BMP-mediated repression in hair follicle stem cell activation. Cell Stem Cell 10: 63-75.
79. Ouji Y, Yoshikawa M, Shiroi A, Ishizaka S. 2006. Promotion of hair follicle development and trichogenesis by Wnt10bin cultured embryonic skin and inreconstituted skin. Biochem Biophys Res Commun 345: 581-587.
80. Ouji Y, Yoshikawa M, Moriya K, Nishiofuku M, Matsuda R, Ishizaka S. 2008. Wnt-10b, uniquely among Wnts, promotes epithelial differentiation and shaft growth. Biochem Biophys Res Commun 367: 299-304.
81. Owens DM, Watt FM. 2003. Contribution of stem cells and differentiated cellsto epidermal tumours. Nat Rev Cancer 3: 444-451.
82. Pálmer HG, Anjos-Afonso F, Carmeliet G, Takeda H, Watt FM. 2008. The vitamin D receptor is a Wnt effector that controls hair follicle differentiation and specifies tumor type in adult epidermis. PLoS ONE 3: e1483.
83. Paus R, Müller-Röver S, van der Veen C, Maurer M, Eichmüller S, Ling G, Hofmann U, Foitzik K, Mecklenburg L, Handjiski B. 1999. A comprehensive guide for the recognition and classification of distinct stages of hair follicle morphogenesis. J Invest Dermatol 113: 523-532.
84. Plikus MV, Mayer JA, la Cruz de D, Baker RE, Maini PK, Maxson R, Chuong C-M. 2008. Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration. Nature 451: 340-344.
85. Rabbani P, Takeo M, Chou W, Myung P, Bosenberg M, Chin L, Taketo MM, Ito M. 2011. Coordinated activation of Wnt in epithelial and melanocyte stem cells initiates pigmented hair regeneration. Cell 145: 941-955.
86. Rawles ME. 1947. Origin of pigment cells from the neural crest in the mouse embryo. Physiol Zool 20: 248-266.
87. Reddy S, Andl T, Bagasra A, Lu MM, Epstein DJ, Morrisey EE, Millar SE. 2001. Characterization of Wnt gene expression in developing and postnatal hair follicles and identification of Wnt5a as a target of Sonic hedgehog in hair follicle morphogenesis. Mech Dev 107: 69-82.
88. Reddy ST, Andl T, Lu M-M, Morrisey EE, Millar SE. 2004. Expression of Frizzled genes in developing and postnatal hair follicles. J Invest Dermatol 123: 275-282.
89. Rhee H, Polak L, Fuchs E. 2006. Lhx2 maintains stem cell character in hair follicles. Science 312: 1946.
90. Saito H, Yasumoto K-I, Takeda K, Takahashi K, Yamamoto H, Shibahara S. 2003. Microphthalmia-associated transcription factor in the Wnt signaling pathway. Pigment Cell Res 16: 261-265.
91. Salto-Tellez M, Peh BK, Ito K, Tan SH, Chong PY, Han HC, Tada K, Ong WY, Soong R, Voon DC, et al. 2006. RUNX3 protein is overexpressed in human basal cell carcinomas. Oncogene 25: 7646-7649.
92. Schmidt-Ullrich R, Paus R. 2005. Molecular principles of hair follicle induction and morphogenesis. Bioessays 27: 247-261.
93. Schneider MR, Paus R. 2010. Sebocytes, multifaceted epithelial cells: Lipid production and holocrine secretion. Int J Biochem Cell Biol 42: 181-185.
94. Schneider MR, Schmidt-Ullrich R, Paus R. 2009. The hair follicle as a dynamic miniorgan. Curr Biol 19: R132-R142.
95. Sick S, Reinker S, Timmer J, Schlake T. 2006. WNTand DKK determine hair follicle spacing through a reaction-diffusion mechanism. Science 314: 1447.
96. Silva-Vargas V, Lo Celso C, Giangreco A, Ofstad T, Prowse DM, Braun KM, Watt FM. 2005. b-catenin and Hedgehog signal strength can specify number and location of hair follicles in adult epidermis without recruitment of bulge stem cells. Dev Cell 9: 121-131.
97. Stevens JR, Miranda-Carboni GA, Singer MA, Brugger SM, Lyons KM, Lane TF. 2010. Wnt10b deficiency results in age-dependent loss of bone mass and progressive reduction of mesenchymal progenitor cells. J Bone Miner Res 25: 2138-2147.
98. Takeda K, Yasumoto K, Takada R, Takada S, Watanabe K, Udono T, Saito H, Takahashi K, Shibahara S. 2000. Induction of melanocyte-specific microphthalmia-associated transcription factor by Wnt-3a. J Biol Chem 275: 14013-14016.
99. Takeda H, Lyle S, Lazar AJF, Zouboulis CC, Smyth I, Watt FM. 2006. Human sebaceous tumors harbor inactivating mutations in LEF1. Nat Med 12: 395-397.
100. Takeuchi S, Takeda K, Oishi I, Nomi M, Ikeya M, Itoh K, Tamura S, Ueda T, Hatta T, Otani H, et al. 2000. Mouse Ror2 receptor tyrosine kinase is required for the heart development and limb formation. Genes Cells 5: 71-78.
101. Tanimura S, Tadokoro Y, Inomata K, Binh NT, Nishie W, Yamazaki S, Nakauchi H, Tanaka Y, McMillan JR, Sawamura D, et al. 2011. Hair follicle stem cells provide a functional niche for melanocyte stem cells. Cell Stem Cell 8: 177-187.
102. Teulière J, Faraldo M, Shtutman M, Birchmeier W, Huelsken J, Thiery J, Glukhova M. 2004. b-Catenin-dependent and -independent effects of DN-plakoglobin on epidermal growth and differentiation. Mol Cell Biol 24: 8649-8661.
103. Ting-Berreth SA, Chuong CM. 1996a. Local deliveryof TGF b2 can substitute for placode epithelium to induce mesenchymal condensation during skin appendage morphogenesis. Dev Biol 179: 347-359.
104. Ting-Berreth SA, Chuong CM. 1996b. Sonic Hedgehog in feather morphogenesis: Induction of mesenchymal condensation and association with cell death. Dev Dyn 207: 157-170.
105. Tumbar T, Guasch G, Greco V, Blanpain C, Lowry WE, Rendl M, Fuchs E. 2004. Defining the epithelial stem cell niche in skin. Science 303: 359-363.
106. van de Wetering M, Sancho E, Verweij C, de Lau W, Oving I, Hurlstone A, van der Horn K, Batlle E, Coudreuse D, Haramis AP, et al. 2002. The b-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 111: 241-250.
107. van Genderen C, Okamura RM, Farinas I, Quo RG, Parslow TG, Bruhn L, Grosschedl R.1994. Development ofseveral organs that require inductive epithelial-mesenchymal interactionsis impaired in LEF-1-deficient mice. Genes Dev 8: 2691-2703.
108. Van Mater D, Kolligs FT, Andrzej A, Dlugosz, Fearon ER. 2003. Transient activation of b-catenin signaling in cutaneous keratinocytes is sufficient to trigger the active growth phase of the hair cycle in mice. Genes Dev 17: 1219-1224.
109. Vasioukhin V, Degenstein L, Wise B, Fuchs E. 1999. The magical touch: Genome targeting in epidermal stem cells induced by tamoxifen application to mouse skin. Proc Natl Acad Sci 96: 8551-8556.
110. Vidal VPI, Chaboissier M-C, Lützkendorf S, Cotsarelis G, Mill P, Hui C-C, Ortonne N, Ortonne J-P, Schedl A. 2005. Sox9 is essential for outer root sheath differentiation and the formation of the hair stem cell compartment. Curr Biol 15: 1340-1351.
111. Waikel RL, Kawachi Y, Waikel PA, Wang XJ, Roop DR. 2001. Deregulated expressionofc-Myc depletes epidermal stem cells. Nat Genet 28: 165-168.
112. Watt FM, Collins CA. 2008. Role of b-catenin in epidermal stem cell expansion, lineage selection, and cancer. Cold Spring Harbor Symp Quant Biol 73: 503-512.
113. Watt FM, Frye M, Benitah SA. 2008. MYC in mammalian epidermis: How can an oncogene stimulate differentiation? Nat Rev Cancer 8: 234-242.
114. White RM, Zon LI. 2008. Melanocytes in development, regeneration, and cancer. Cell Stem Cell 3: 242-252.
115. Widelitz RB, Jiang TX, Chen CW, Stott NS, Jung HS, Chuong CM. 1999. Wnt-7a in feather morphogenesis: Involvement of anterior-posterior asymmetry and proximal-distal elongation demonstrated with an in vitro reconstitution model. Development 126: 2577-2587.
116. Wilson PA, Hemmati-Brivanlou A. 1995. Induction of epidermis and inhibition of neural fate by Bmp-4. Nature 376: 331-333.
117. Wilson SI, Rydström A, Trimborn T, Willert K, Nusse R, Jessell TM, Edlund T. 2001. The status of Wnt signalling regulates neural and epidermal fates in the chick embryo. Nature 411: 325-330.
118. Yamaguchi TP, Bradley A, McMahon AP, Jones S. 1999. A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development 126: 1211-1223.
119. Yamaguchi Y, Itami S, Watabe H, Yasumoto K-I, AbdelMalek ZA, Kubo T, Rouzaud F, Tanemura A, Yoshikawa K, Hearing VJ. 2004. Mesenchymal-epithelial interactions in the skin: Increased expression of dickkopf1 by palmoplantar fibroblasts inhibits melanocyte growth and differentiation. J Cell Biol 165: 275-285.
120. Yang SH, Andl T, Grachtchouk V, Wang A, Liu J, Syu L-J, Ferris J, Wang TS, Glick AB, Millar SE, et al. 2008. Pathological responses to oncogenic Hedgehog signaling in skin are dependent on canonical Wnt/b3-catenin signaling. Nat Genet 40: 1130-1135.
121. Yasumoto K-I, Takeda K, Saito H, Watanabe K-I, Takahashi K, Shibahara S. 2002. Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling. EMBO J 21: 2703-2714.
122. Yuhki M, Yamada M, Kawano M, Iwasato T, Itohara S, Yoshida H, Ogawa M, Mishina Y. 2004. BMPR1A signaling is necessary for hair follicle cycling and hair shaft differentiation in mice. Development 131: 1825-1833.
123. Zhang J, He XC, Tong W-G, Johnson T, Wiedemann LM, Mishina Y, Feng JQ, Li L. 2006. Bone morphogenetic protein signaling inhibits hair follicle anagen induction by restricting epithelial stem/progenitor cell activation and expansion. Stem Cells 24: 2826-2839.
124. Zhang Y, Tomann P, Andl T, Gallant NM, Huelsken J, Jerchow B, Birchmeier W, Paus R, Piccolo S, Mikkola ML, et al. 2009. Reciprocal requirements for EDA/EDAR/NFkB and Wnt/b-catenin signaling pathways in hair follicle induction. Dev Cell 17: 49-61.
125. Zhou P, Byrne C, Jacobs J, Fuchs E. 1995.Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate. Genes Dev 9: 700-713.
126. Zhu AJ, Watt FM. 1999. b-catenin signalling modulates proliferative potential of human epidermal keratinocytes independently of intercellular adhesion. Development 126: 2285-2298.