Mutant p63 causes defective expansion of ectodermal progenitor cells and impaired FGF signalling in AEC syndrome

EMBO Molecular Medicine

Volumn 4, Issue 3, 2012, Pages 192-205

  Ferone, Giustina ^a   Thomason, Helen A ^b,k   Antonini, Dario ^c   De Rosa, Laura ^c,l   Hu, Bing ^d   Gemei, Marica ^c   Zhou, Huiqing ^e   Ambrosio, Raffaele ^a   Rice, David P ^f   Acampora, Dario ^c,g   van Bokhoven, Hans ^e   Del Vecchio, Luigi ^c   Koster, Maranke I ^h   Tadini, Gianluca ⁱ   Spencer Dene, Bradley ^j   Dixon, Michael ^b   Dixon, Jill ^b   Missero, Caterina ^c  

^a IRCCS SDN   (Italy)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

^c CEINGE BIOTECNOLOGIE AVANZATE   (Italy)

^d UNIVERSITY OF LAUSANNE   (Switzerland)

^e RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^f UNIVERSITY OF HELSINKI   (Finland)

^g INSTITUTE OF GENETICS AND BIOPHYSICS ADRIANO BUZZATI TRAVERSO   (Italy)

^h UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

ⁱ UNIVERSITY OF MILAN   (Italy)

^j IMPERIAL CANCER RESEARCH FUND   (United Kingdom)

^k UNIVERSITY OF MANCHESTER   (United Kingdom)

^l UNIVERSITY OF MODENA AND REGGIO EMILIA   (Italy)

more..

Author keywords

AEC syndrome; Epidermis; FGF signalling; P63 knock in; P63 target genes

Indexed keywords

FIBROBLAST GROWTH FACTOR RECEPTOR 2; FIBROBLAST GROWTH FACTOR RECEPTOR 3; KERATINOCYTE GROWTH FACTOR; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN P63;

AEC SYNDROME; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL DENSITY; CELL EXPANSION; CELL MATURATION; CELL PROLIFERATION; CELL RENEWAL; CONTROLLED STUDY; DOMINANT GENE; ECTODERM; EPIDERMIS; EPITHELIUM CELL; FEMALE; GENE FUNCTION; GENE MUTATION; HUMAN; HUMAN CELL; IN VIVO STUDY; KERATINOCYTE; MALE; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; RECEPTOR DOWN REGULATION; SIGNAL TRANSDUCTION; STEM CELL;

ANIMALS; CELL PROLIFERATION; CLEFT LIP; CLEFT PALATE; ECTODERM; ECTODERMAL DYSPLASIA; EYE ABNORMALITIES; EYELIDS; FEMALE; FIBROBLAST GROWTH FACTORS; HUMANS; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICE, TRANSGENIC; MUTATION; SIGNAL TRANSDUCTION; STEM CELLS; TRANSCRIPTION FACTORS; TUMOR SUPPRESSOR PROTEINS;

EID: 84863229693     PISSN: 17574676     EISSN: 17574684     Source Type: Journal    
DOI: 10.1002/emmm.201100199     Document Type: Article

References (52)

1. Antonini D, Russo MT, De Rosa L, Gorrese M, Del Vecchio L, Missero C (2010) Transcriptional repression of miR-34 family contributes to p63-mediated cell cycle progression in epidermal cells. J Invest Dermatol 130: 1249-1257.
2. Bell O, Tiwari VK, Thoma NH, Schubeler D (2011) Determinants and dynamics of genome accessibility. Nat Rev Genet 12: 554-564.
3. Browne G, Cipollone R, Lena AM, Serra V, Zhou H, van Bokhoven H, Dotsch V, Merico D, Mantovani R, Terrinoni A et al (2011) Differential altered stability and transcriptional activity of DeltaNp63 mutants in distinct ectodermal dysplasias. J Cell Sci 124: 2200-2207.
4. Candi E, Rufini A, Terrinoni A, Giamboi-Miraglia A, Lena AM, Mantovani R, Knight R, Melino G (2007) DeltaNp63 regulates thymic development through enhanced expression of FgfR2 and Jag2. Proc Natl Acad Sci USA 104: 11999-12004.
5. Carroll DK, Carroll JS, Leong CO, Cheng F, Brown M, Mills AA, Brugge JS, Ellisen LW (2006) p63 regulates an adhesion programme and cell survival in epithelial cells. Nat Cell Biol 8: 551-561.
6. Cha JY, Maddileti S, Mitin N, Harden TK, Der CJ (2009) Aberrant receptor internalization and enhanced FRS2-dependent signaling contribute to the transforming activity of the fibroblast growth factor receptor 2 IIIb C3 isoform. J Biol Chem 284: 6227-6240.
7. Chitayat D, Babul R, Silver MM, Jay V, Teshima IE, Babyn P, Becker LE (1996) Terminal deletion of the long arm of chromosome 3 [46, XX, del(3)(q27->qter)]. Am J Med Genet 61: 45-48.
8. De Moerlooze L, Spencer-Dene B, Revest JM, Hajihosseini M, Rosewell I, Dickson C (2000) An important role for the IIIb isoform of fibroblast growth factor receptor 2 (FGFR2) in mesenchymal-epithelial signalling during mouse organogenesis. Development (Cambridge, England) 127: 483-492.
9. De Rosa L, Antonini D, Ferone G, Russo MT, Yu PB, Han R, Missero C (2009) p63 suppresses non-epidermal lineage markers in a bone morphogenetic protein-dependent manner via repression of Smad7. J Biol Chem 284: 30574-30582.
10. Della Gatta G, Bansal M, Ambesi-Impiombato A, Antonini D, Missero C, di Bernardo D (2008) Direct targets of the TRP63 transcription factor revealed by a combination of gene expression profiling and reverse engineering. Genome Res 18: 939-948.
11. Dishop MK, Bree AF, Hicks MJ (2009) Pathologic changes of skin and hair in ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome. Am J Med Genet 149A: 1935-1941.
12. Farrington F, Lausten L (2009) Oral findings in ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC) syndrome. Am J Med Genet 149A: 1907-1909.
13. Fete M, vanBokhoven H, Clements SE, McKeon F, Roop DR, Koster MI, Missero C, Attardi LD, Lombillo VA, Ratovitski E et al (2009) International Research Symposium on Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate (AEC) Syndrome. Am J Med Genet 149A: 1885-1893.
14. Fomenkov A, Huang YP, Topaloglu O, Brechman A, Osada M, Fomenkova T, Yuriditsky E, Trink B, Sidransky D, Ratovitski E (2003) P63 alpha mutations lead to aberrant splicing of keratinocyte growth factor receptor in the Hay-Wells syndrome. J Biol Chem 278: 23906-23914.
15. Fuchs E (2009) Finding one's niche in the skin. Cell Stem Cell 4: 499-502.
16. Julapalli MR, Scher RK, Sybert VP, Siegfried EC, Bree AF (2009) Dermatologic findings of ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome. Am J Med Genet 149A: 1900-1906.
17. Koster MI, Kim S, Mills AA, DeMayo FJ, Roop DR (2004) p63 is the molecular switch for initiation of an epithelial stratification program. Genes Dev 18: 126-131.
18. Koster MI, Dai D, Marinari B, Sano Y, Costanzo A, Karin M, Roop DR (2007) p63 induces key target genes required for epidermal morphogenesis. Proc Natl Acad Sci USA 104: 3255-3260.
19. Koster MI, Marinari B, Payne AS, Kantaputra PN, Costanzo A, Roop DR (2009) DeltaNp63 knockdown mice: a mouse model for AEC syndrome. Am J Med Genet 149A: 1942-1947.
20. Kouwenhoven EN, van Heeringen SJ, Tena JJ, Oti M, Dutilh BE, Alonso ME, de la Calle-Mustienes E, Smeenk L, Rinne T, Parsaulian L et al (2010) Genome-wide profiling of p63 DNA-binding sites identifies an element that regulates gene expression during limb development in the 7q21 SHFM1 locus. PLoS Genet 6: e1001065.
21. Laurikkala J, Mikkola ML, James M, Tummers M, Mills AA, Thesleff I (2006) p63 regulates multiple signalling pathways required for ectodermal organogenesis and differentiation. Development (Cambridge, England) 133: 1553-1563.
22. Leboeuf M, Terrell A, Trivedi S, Sinha S, Epstein JA, Olson EN, Morrisey EE, Millar SE (2011) Hdac1 and Hdac2 act redundantly to control p63 and p53 functions in epidermal progenitor cells. Dev Cell 19: 807-818.
23. Liu Y, Lyle S, Yang Z, Cotsarelis G (2003) Keratin 15 promoter targets putative epithelial stem cells in the hair follicle bulge. J Invest Dermatol 121: 963-968.
24. Lopardo T, Lo Iacono N, Marinari B, Giustizieri ML, Cyr DG, Merlo G, Crosti F, Costanzo A, Guerrini L (2008) Claudin-1 is a p63 target gene with a crucial role in epithelial development. PLoS One 3: e2715.
25. Mandinova A, Kolev V, Neel V, Hu B, Stonely W, Lieb J, Wu X, Colli C, Han R, Pazin MJ et al (2009) A positive FGFR3/FOXN1 feedback loop underlies benign skin keratosis versus squamous cell carcinoma formation in humans. J Clin Invest 119: 3127-3137.
26. Marinari B, Ballaro C, Koster MI, Giustizieri ML, Moretti F, Crosti F, Papoutsaki M, Karin M, Alema S, Chimenti S et al (2009) IKKalpha is a p63 transcriptional target involved in the pathogenesis of ectodermal dysplasias. J Invest Dermatol 129: 60-69.
27. McGrath JA, Duijf PH, Doetsch V, Irvine AD, de Waal R, Vanmolkot KR, Wessagowit V, Kelly A, Atherton DJ, Griffiths WA et al (2001) Hay-Wells syndrome is caused by heterozygous missense mutations in the SAM domain of p63. Hum Mol Genet 10: 221-229.
28. Mills AA, Zheng B, Wang XJ, Vogel H, Roop DR, Bradley A (1999) p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature 398: 708-713.
29. Moretti F, Marinari B, Lo Iacono N, Botti E, Giunta A, Spallone G, Garaffo G, Vernersson-Lindahl E, Merlo G Mills AA et al (2010) A regulatory feedback loop involving p63 and IRF6 links the pathogenesis of 2 genetically different human ectodermal dysplasias. J Clin Invest 120: 1570-1577.
30. Nguyen BC, Lefort K, Mandinova A, Antonini D, Devgan V, Della G, Koster G, Zhang MI, Wang Z, Tommasi J et al (2006) Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation. Genes Dev 20: 1028-1042.
31. Nowak JA, Polak L, Pasolli HA, Fuchs E (2008) Hair follicle stem cells are specified and function in early skin morphogenesis. Cell Stem Cell 3: 33-43.
32. Payne AS, Yan AC, Ilyas E, Li W, Seykora JT, Young TL, Pawel BR, Honig PJ, Camacho J, Imaizumi S et al (2005) Two novel TP63 mutations associated with the ankyloblepharon, ectodermal defects, and cleft lip and palate syndrome: a skin fragility phenotype. Arch Dermatol 141: 1567-1573.
33. Petiot A, Conti FJ, Grose R, Revest JM, Hodivala-Dilke KM, Dickson C (2003) A crucial role for Fgfr2-IIIb signalling in epidermal development and hair follicle patterning. Development (Cambridge, England) 130: 5493-5501.
34. Rama P, Matuska S, Paganoni G, Spinelli A, De Luca M, Pellegrini G (2010) Limbal stem-cell therapy and long-term corneal regeneration. N Engl J Med 363: 147-155.
35. Revest JM, Spencer-Dene B, Kerr K, De Moerlooze L, Rosewell I, Dickson C (2001) Fibroblast growth factor receptor 2-IIIb acts upstream of Shh and Fgf4 and is required for limb bud maintenance but not for the induction of Fgf8, Fgf10, Msx1, or Bmp4. Dev Biol 231: 47-62.
36. Rice R, Spencer-Dene B, Connor EC, Gritli-Linde A, McMahon AP, Dickson C, Thesleff I, Rice DP (2004) Disruption of Fgf10/Fgfr2b-coordinated epithelial-mesenchymal interactions causes cleft palate. J Clin Invest 113: 1692-1700.
37. Rinne T, Bolat E, Meijer R, Scheffer H, van Bokhoven H (2009) Spectrum of p63 mutations in a selected patient cohort affected with ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC). Am J Med Genet 149A: 1948-1951.
38. Senoo M, Pinto F, Crum CP, McKeon F (2007) p63 Is essential for the proliferative potential of stem cells in stratified epithelia. Cell 129: 523-536.
39. Stachelscheid H, Ibrahim H, Koch L, Schmitz A, Tscharntke M, Wunderlich FT, Scott J, Michels C, Wickenhauser C, Haase I et al (2008) Epidermal insulin/IGF-1 signalling control interfollicular morphogenesis and proliferative potential through Rac activation. EMBO J 27: 2091-2101.
40. Strachan LR, Scalapino KJ, Lawrence HJ, Ghadially R (2008) Rapid adhesion to collagen isolates murine keratinocytes with limited long-term repopulating ability in vivo despite high clonogenicity in vitro. Stem Cells 26: 235-243.
41. Su X, Cho MS, Gi YJ, Ayanga BA, Sherr CJ, Flores ER (2009) Rescue of key features of the p63-null epithelial phenotype by inactivation of Ink4a and Arf. EMBO J 28: 1904-1915.
42. Tani H, Morris RJ, Kaur P (2000) Enrichment for murine keratinocyte stem cells based on cell surface phenotype. Proc Natl Acad Sci USA 97: 10960-10965.
43. Thomason HA, Dixon MJ, Dixon J (2008) Facial clefting in Tp63 deficient mice results from altered Bmp4, Fgf8 and Shh signaling. Dev Biol 321: 273-282.
44. Truong AB, Kretz M, Ridky TW, Kimmel R, Khavari PA (2006) p63 regulates proliferation and differentiation of developmentally mature keratinocytes. Genes Dev 20: 3185-3197.
45. 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.
46. Vidal VP, Chaboissier MC, Lutzkendorf S, Cotsarelis G, Mill P, Hui CC, Ortonne N, Ortonne JP, 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.
47. Vigano MA, Lamartine J, Testoni B, Merico D, Alotto D, Castagnoli C, Robert A, Candi E, Melino G, Gidrol X et al (2006) New p63 targets in keratinocytes identified by a genome-wide approach. EMBO J 25: 5105-5116.
48. Watt FM, Jensen KB (2009) Epidermal stem cell diversity and quiescence. EMBO Mol Med 1: 260-267.
49. Wu G, Nomoto S, Hoque MO, Dracheva T, Osada M, Lee CC, Dong SM, Guo Z, Benoit N, Cohen Y et al (2003) DeltaNp63alpha and TAp63alpha regulate transcription of genes with distinct biological functions in cancer and development. Cancer Res 63: 2351-2357.
50. Yang A, Kaghad M, Wang Y, Gillett E, Fleming MD, Dotsch V, Andrews NC, Caput D, McKeon F (1998) p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell 2: 305-316.
51. Yang A, Schweitzer R, Sun D, Kaghad M, Walker N, Bronson RT, Tabin C, Sharpe A, Caput D, Crum C et al (1999) p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature 398: 714-718.
52. Yang A, Zhu Z, Kapranov P, McKeon F, Church GM, Gingeras TR, Struhl K (2006) Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells. Mol Cell 24: 593-602.