Abstract
• Eda-A1/Edar/Edaradd/NF-κB is a key signaling pathway for hair follicle morphogenesis.
• Hairless is a critical transcription factor to control the catagen phase of the hair cycle.
• FOXN1 is involved in regulating the expression of hair keratin genes.
• Switching of two classical cadherin members in the hair follicle placode is an important event for hair follicle development.
• EEM syndrome (ectodermal dysplasia, ectrodactyly, macular dystrophy), Naxos disease (palmoplantar keratoderma with arrhythmogenic right ventricular cardiomyopathy and woolly hair) and Clouston syndrome (hidrotic ectodermal dysplasia) are molecularly well characterized.
• Desmosomal components maintain hair follicle structure and differentiation.
• Involvement of gap junction proteins in hair diseases is reported.
• LIPH (membrane-associated phosphatidic acid-selective phospholipase A1 alpha) and P2RY5 are new candidate genes for congenital hair disorders.
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References
Ahmad W, Faiyaz ul Haque M, Brancolini V et al (1998) Alopecia universalis associated with a mutation in the human hairless gene. Science 279:720–724
Ahmad W, Panteleyev AA, Sundberg JP et al (1998) Molecular basis for the rhino (hrrh-8J) phenotype: a nonsense mutation in the mouse hairless gene. Genomics 53:383–386
Angst BD, Marcozzi C, Magee AI (2001) The cadherin superfamily: diversity in form and function. J Cell Sci 114:629–641
Armstrong DK, McKenna KE, Purkis PE et al (1999) Haploinsufficiency of desmoplakin causes a striate subtype of palmoplantar keratoderma. Hum Mol Genet 8:143–148
Bayes M, Hartung AJ, Ezer S et al (1998) The anhidrotic ectodermal dysplasia gene (EDA) undergoes alternative splicing and encodes ectodysplasin-A with deletion mutations in collagenous repeats. Hum Mol Genet 7:1661–1669
Bazzi H, Kljuic A, Christiano AM et al (2004) Intragenic deletion in the Desmoglein 4 gene underlies the skin phenotype in the Iffa Credo “hairless” rat. Differentiation 72:450–464
Bazzi H, Getz A, Mahoney MG et al (2006) Desmoglein 4 is expressed in highly differentiated keratinocytes and trichocytes in human epidermis and hair follicle. Differentiation; 74:129–140
Bergman R, Sprecher E (2005) Histopathological and ultrastructural study of ectodermal dysplasia/skin fragility syndrome. Am J Dermatopathol 27:333–338
Betz RC, Lee YA, Bygum A et al (2000) A gene for hypotrichosis simplex of the scalp maps to chromosome 6p21.3. Am J Hum Genet 66:1979–1983
Bierkamp C, Mclaughlin KJ, Schwarz H et al (1996) Embryonic heart and skin defects in mice lacking plakoglobin. Dev Biol 180:780–785
Bierkamp C, Schwarz H, Huber O et al (1999) Desmosomal localization of beta-catenin in the skin of plakoglobin null-mutant mice. Development 126:371–381
Blanpain C, Lowry WE, Geoghegan A et al (2004) Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell 118:635–648
Brooke HC (1926) Hairless mice. J Hered 17:173–174
Cachon-Gonzalez MB, Fenner S, Coffin JM et al (1994) Structure and expression of the hairless gene of mice. Proc Natl Acad Sci U S A 91:7717–7721
Celli J, Duijf P, Hamel B et al (1999) Heterozygous germline mutations in the p53 homolog p63 are the cause of EEC syndrome. Cell 99:143–153
Cichon S, Anker M, Vogt IR et al (1998) Cloning, genomic organization, alternative transcripts and mutational analysis of the gene responsible for autosomal recessive universal congenital alopecia. Hum Mol Genet 7:1671–1679
Common JE, Becker D, Di WL et al (2002) Functional studies of human skin disease- and deafness-associated connexin 30 mutations. Biochem Biophys Res Commun 298:651–656
Coonar AS, Protonotarios N, Tsatsopoulou A et al (1998) Gene for arrhythmogenic right ventricular cardiomyopathy with diffuse nonepidermolytic palmoplantar keratoderma and woolly hair (Naxos disease) maps to 17q21. Circulation 97:2049–2058
Cowin P, Kapprell HP, Franke WW et al (1986) Plakoglobin: a protein common to different kinds of intercellular adhering junctions. Cell 46:1063–1073
Cui CY, Durmowicz M, Ottolenghi C et al (2003) Inducible mEDA-A1 transgene mediates sebaceous gland hyperplasia and differential formation of two types of mouse hair follicles. Hum Mol Genet 12:2931–2940
Cui CY, Hashimoto T, Grivennikov SI et al (2006) Ectodysplasin regulates the lymphotoxin-beta pathway for hair differentiation. Proc Natl Acad Sci USA 103:9142–9147
Djabali K, Martinez-Mir A, Horev L et al (2002) Evidence for extensive locus heterogeneity in Naxos disease. J Invest Dermatol 118:557–560
Eder AM, Sasagawa T, Mao M et al (2000) Constitutive and lysophosphatidic acid (LPA)-induced LPA production: role of phospholipase D and phospholipase A2. Clin Cancer Res 6:2482–2491
Elomaa O, Pulkkinen K, Hannelius U et al (2001) Ectodysplasin is released by proteolytic shedding and binds to the EDAR protein. Hum Mol Genet 10:953–962
Essenfelder GM, Bruzzone R, Lamartine J et al (2004) Connexin30 mutations responsible for hidrotic ectodermal dysplasia cause abnormal hemichannel activity. Hum Mol Genet 13:1703–1714
Essenfelder GM, Larderet G, Waksman G et al (2005) Gene structure and promoter analysis of the human GJB6 gene encoding connexin 30. Gene 350:33–40
Ferguson BM, Brockdorff N, Formstone E et al (1997) Cloning of Tabby, the murine homolog of the human EDA gene: evidence for a membrane-associated protein with a short collagenous domain. Hum Mol Genet 6:1589–1594
Flanagan SP (1966) “Nude”, a new hairless gene with pleiotropic effects in the mouse. Genet Res 8:295–309
Fourcade O, Simon MF, Viode C et al (1995) Secretory phospholipase A2 generates the novel lipid mediator lysophosphatidic acid in membrane microvesicles shed from activated cells. Cell 80:919–927
Frank J, Pignata C, Panteleyev AA et al (1999) Exposing the human nude phenotype. Nature 398:473–474
Fuchs E, Raghavan S (2002) Getting under the skin of epidermal morphogenesis. Nat Rev Genet 3:199–209
Gaide O, Schneider P (2003) Permanent correction of an inherited ectodermal dysplasia with recombinant EDA. Nat Med 9:614–618
Gallicano GI, Kouklis P, Bauer C et al (1998) Desmoplakin is required early in development for assembly of desmosomes and cytoskeletal linkage. J Cell Biol 143:2009–2022
Gallinaro H, Jonca N, Langbein L et al (2004) A 4.2 kb upstream region of the human corneodesmosin gene directs site-specific expression in hair follicles and hyperkeratotic epidermis of transgenic mice. J Invest Dermatol 122:730–738
Goodwin M, Yap AS (2004) Classical cadherin adhesion molecules: coordinating cell adhesion, signaling and the cytoskeleton. J Mol Histol 35:839–844
Green KJ, Gaudry CA (2000) Are desmosomes more than tethers for intermediate filaments? Nat Rev Mol Cell Biol 1:208–216
Green KJ, Parry DA, Steinert PM et al (1990) Structure of the human desmoplakins. Implications for function in the desmosomal plaque. J Biol Chem 265:11406–11407
Gumbiner BM (2005) Regulation of cadherin-mediated adhesion in morphogenesis. Nat Rev Mol Cell Biol 6:622–634
Headon DJ, Overbeek PA (1999) Involvement of a novel Tnf receptor homologue in hair follicle induction. Nat Genet 22:370–374
Headon DJ, Emmal SA, Ferguson BM et al (2001) Gene defect in ectodermal dysplasia implicates a death domain adapter in development. Nature 414:913–916
Herzog H, Darby K, Hort YJ et al (1996) Intron 17 of the human retinoblastoma susceptibility gene encodes an actively transcribed G protein-coupled receptor gene. Genome Res 6:858–861.
Hirai Y, Nose A, Kobayashi S et al (1989) Expression and role of E- and P-cadherin adhesion molecules in embryonic histogenesis. II. Skin morphogenesis. Development 105:271–277
Hsieh JC, Sisk JM, Jurutka PW et al (2003) Physical and functional interaction between the vitamin D receptor and hairless corepressor, two proteins required for hair cycling. J Biol Chem 278:38665–38674
Hughes MR, Malloy PJ, Kieback DG et al (1988) Point mutations in the human vitamin D receptor gene associated with hypocalcemic rickets. Science 242:1702–1705
Hutchinson PE, Cairns RJ, Wells RS (1974) Woolly hair. Clinical and general aspects. Trans St Johns Hosp Dermatol Soc 60:160–177.
Irvine AD, Christiano AM (2001) Hair on a gene string: recent advances in understanding the molecular genetics of hair loss. Exp Dermatol 26:59–71
Jahoda CA, Kljuic A, O’Shaughnessy R et al (2004) The lanceolate hair rat phenotype results from a missense mutation in a calcium coordinating site of the desmoglein 4 gene. Genomics 83:747–756
Jamora C, DasGupta R, Kocieniewski P et al (2003) Links between signal transduction, transcription and adhesion in epithelial bud development. Nature 422:317–322
Jan AY, Amin S, Ratajczak P et al (2004) Genetic heterogeneity of KID syndrome: identification of a Cx30 gene (GJB6) mutation in a patient with KID syndrome and congenital atrichia. J Invest Dermatol 122:1108–1113
Jin W, Broedl UC, Monajemi H et al (2002) Lipase H, a new member of the triglyceride lipase family synthesized by the intestine. Genomics 80:268–273
Johns SA, Soullier S, Rashbass P et al (2005) Foxn1 is required for tissue assembly and desmosomal cadherin expression in the hair shaft. Dev Dyn 232:1062–1068
Kamibayashi Y, Oyamada Y, Mori M et al (1995) Aberrant expression of gap junction proteins (connexins) is associated with tumor progression during multistage mouse skin carcinogenesis in vivo. Carcinogenesis 16:1287–1297
Kazantseva A, Goltsov A, Zinchenko R et al (2006) Human hair growth deficiency is linked to a genetic defect in the phospholipase gene LIPH. Science 314:982–985
Kere J, Srivastava AK, Montonen O et al (1996) X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein. Nat Genet 13:409–416
Kjaer KW, Hansen L, Eiberg H et al (2004) Novel Connexin 43 (GJA1) mutation causes oculo-dento-digital dysplasia with curly hair. Am J Med Genet A 127:152–157
Kjaer KW, Hansen L, Schwabe GC et al (2005) Distinct CDH3 mutations cause ectodermal dysplasia, ectrodactyly, macular dystrophy (EEM syndrome). J Med Genet 42:292–298
Kljuic A, Bazzi H, Sundberg JP et al (2003) Desmoglein 4 in hair follicle differentiation and epidermal adhesion: evidence from inherited hypotrichosis and acquired pemphigus vulgaris. Cell 113:249–260
Kouklis PD, Hutton E, Fuchs E (1994) Making a connection: direct binding between keratin intermediate filaments and desmosomal proteins. J Cell Biol 127:1049–1060
Kowalczyk AP, Bornslaeger EA, Borgwardt JE et al (1997) The amino-terminal domain of desmoplakin binds to plakoglobin and clusters desmosomal cadherin-plakoglobin complexes. J Cell Biol 139:773–784
Kowalczyk AP, Hatzfeld M, Bornslaeger EA et al (1999) The head domain of plakophilin-1 binds to desmoplakin and enhances its recruitment to desmosomes. Implications for cutaneous disease. J Biol Chem 274:18145–18148
Labarthe MP, Bosco D, Saurat JH et al (1998) Upregulation of connexin 26 between keratinocytes of psoriatic lesions. J Invest Dermatol 111:72–76
Lamartine J, Munhoz Essenfelder G, Kibar Z et al (2000) Mutations in GJB6 cause hidrotic ectodermal dysplasia. Nat Genet 26:142–144
Langbein L, Schweizer J (2005) Keratins of the human hair follicle. Int Rev Cytol 243:1–78
Langbein L, Rogers MA, Winter H et al (1999) The catalog of human hair keratins. I. Expression of the nine type I members in the hair follicle. J Biol Chem 274:19874–19884
Langbein L, Rogers MA, Winter H et al (2001) The catalog of human hair keratins. II. Expression of the six type II members in the hair follicle and the combined catalog of human type I and II keratins. J Biol Chem 276:35123–35132
Laurikkala J, Mikkola M, Mustonen T et al (2001) TNF signaling via the ligand-receptor pair ectodysplasin and edar controls the function of epithelial signaling centers and is regulated by Wnt and activin during tooth organogenesis. Dev Biol 229:443–455
Laurikkala J, Pispa J, Jung HS et al (2002) Regulation of hair follicle development by the TNF signal ectodysplasin and its receptor Edar. Development 129:2541–2553
Lee D, Prowse DM, Brissette JL (1999) Association between mouse nude gene expression and the initiation of epithelial terminal differentiation. Dev Biol 208:362–374
Lemaitre G, Sivan V, Lamartine J et al (2006) Connexin 30, a new marker of hyperproliferative epidermis. Br J Dermatol 155:844–846
Levy-Nissenbaum E, Betz RC, Frydman M et al (2003) Hypotrichosis simplex of the scalp is associated with nonsense mutations in CDSN encoding corneodesmosin. Nat Genet 34:151–153
McGrath JA (2005) Inherited disorders of desmosomes. Australas J Dermatol 46:221–229
McGrath JA, McMillan JR, Shemanko CS et al (1997) Mutations in the plakophilin 1 gene result in ectodermal dysplasia/skin fragility syndrome. Nat Genet 17:240–244
McKoy G, Protonotarios N, Crosby A et al (2000) Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease). Lancet 355:2119–2124
Meier H, Myers DD, Huebner RJ (1969) Genetic control by the hr-locus of susceptibility and resistance to leukemia. Proc Natl Acad Sci U S A 63:759–766
Meier N, Dear TN, Boehm T (1999) Whn and mHa3 are components of the genetic hierarchy controlling hair follicle differentiation. Mech Dev 89:215–221
Meng JJ, Bornslaeger EA, Green KJ et al (1997) Two-hybrid analysis reveals fundamental differences in direct interactions between desmoplakin and cell type-specific intermediate filaments. J Biol Chem 272:21495–21503
Menton DN, Eisen AZ (1971) Structure and organization of mammalian stratum corneum. J Ultrastruct Res 35:247–64
Meyer B, Bazzi H, Zidek V et al (2004) A spontaneous mutation in the desmoglein 4 gene underlies hypotrichosis in a new lanceolate hair rat model. Differentiation 72:541–547
Millar SE (2002) Molecular mechanisms regulating hair follicle development. J Invest Dermatol 118:216–225
Mills AA, Zheng B, Wang XJ et al (1999) p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature 398:708–713.
Moll I, Kurzen H, Langbein L et al (1997) The distribution of the desmosomal protein, plakophilin 1, in human skin and skin tumors. J Invest Dermatol 108:139–146
Monreal AW, Zonana J, Ferguson B (1998) Identification of a new splice form of the EDA1 gene permits detection of nearly all X-linked hypohidrotic ectodermal dysplasia mutations. Am J Hum Genet 63:380–389
Monreal AW, Ferguson BM, Headon DJ, Street et al (1999) Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia. Nat Genet 22:366–369
Montagutelli X, Hogan ME, Aubin G et al (1996) Lanceolate hair (lah): a recessive mouse mutation with alopecia and abnormal hair. J Invest Dermatol 107:20–25
Moolenaar WH (1999) Bioactive lysophospholipids and their G protein-coupled receptors. Exp Cell Res 253:230–238
Morris RJ, Liu Y, Marles L et al (2004) Capturing and profiling adult hair follicle stem cells. Nat Biotechnol 22:411–417
Morrissey PJ, Parkinson DR, Schwartz RS et al (1980) Immunologic abnormalities in HRS/J mice. I. Specific deficit in T lymphocyte helper function in a mutant mouse. J Immunol 125:1558–1562
Mou C, Jackson B, Schneider P et al (2006) Generation of the primary hair follicle pattern. Proc Natl Acad Sci U S A 103:9075–9080
Muller-Rover S, Tokura Y, Welker P et al (1999) E- and P-cadherin expression during murine hair follicle morphogenesis and cycling. Exp Dermatol 8:237–246
Mustonen T, Pispa J, Mikkola ML et al (2003) Stimulation of ectodermal organ development by Ectodysplasin-A1. Dev Biol 259:123–136
Nehls M, Pfeifer D, Schorpp M et al (1994) New member of the winged-helix protein family disrupted in mouse and rat nude mutations. Nature 372:103–107
Norgett EE, Hatsell SJ, Carvajal-Huerta L et al (2000) Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma. Hum Mol Genet 9:2761–2766
North AJ, Bardsley WG, Hyam J et al (1999) Molecular map of the desmosomal plaque. J Cell Sci 112:4325–4336
Ohyama M, Terunuma A, Tock CL et al (2006) Characterization and isolation of stem cell-enriched human hair follicle bulge cells. J Clin Invest 116:249–260
Oshima H, Rochat A, Kedzia C et al (2001) Morphogenesis and renewal of hair follicles from adult multipotent stem cells. Cell 104:233–245
Panteleyev AA, Thiel R, Wanner R et al (1997) 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCCD) affects keratin 1 and keratin 17 gene expression and differentially induces keratinization in hairless mouse skin. J Invest Dermatol 108:330–335
Panteleyev AA, Ahmad W, Malashenko AM et al (1998) Molecular basis for the rhino Yurlovo (hr(rhY)) phenotype: severe skin abnormalities and female reproductive defects associated with an insertion in the hairless gene. Exp Dermatol 7:281–288
Panteleyev AA, Botchkareva NV, Sundberg JP et al (1999) The role of the hairless (hr) gene in the regulation of hair follicle catagen transformation. Am J Pathol 155:159–171
Panteleyev AA, Paus R, Christiano AM (2000) Patterns of hairless (hr) gene expression in mouse hair follicle morphogenesis and cycling. Am J Pathol 157:1071–1079
Pasternack SM, von Kügelgen I, Aboud KA et al (2008) G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth. Nat Genet 40:329–334.
Paus R, Foitzik K (2004) In search of the “hair cycle clock”: a guided tour. Differentiation 72:489–511
Perrin C, Langbein L, Schweizer J (2004) Expression of hair keratins in the adult nail unit: an immunohistochemical analysis of the onychogenesis in the proximal nail fold, matrix and nail bed. Br J Dermatol 151:362–371
Potter GB, Beaudoin GM 3rd, DeRenzo CL et al (2001) The hairless gene mutated in congenital hair loss disorders encodes a novel nuclear receptor corepressor. Genes Dev 15:2687–2701
Radice GL, Ferreira-Cornwell MC, Robinson SD et al (1997) Precocious mammary gland development in P-cadherin-deficient mice. J Cell Biol 139:1025–1032
Reaume AG, de Sousa PA, Kulkarni S et al (1995) Cardiac malformation in neonatal mice lacking connexin43. Science 267:1831–1834
Richard G (2000) Connexins: a connection with the skin. Exp Dermatol 9:77–96
Richard G, Rouan F, Willoughby CE et al (2002) Missense mutations in GJB2 encoding connexin-26 cause the ectodermal dysplasia keratitis-ichthyosis-deafness syndrome. Am J Hum Genet 70:1341–1348
Rogers MA, Winter H, Langbein L et al (2004) The human type I keratin gene family: characterization of new hair follicle specific members and evaluation of the chromosome 17q21.2 gene domain. Differentiation 72:527–540
Rogers MA, Edler L, Winter H et al (2005) Characterization of new members of the human type II keratin gene family and a general evaluation of the keratin gene domain on chromosome 12q13.13. J Invest Dermatol 124:536–544
Ruiz P, Brinkmann V, Ledermann B et al (1996) Targeted mutation of plakoglobin in mice reveals essential functions of desmosomes in the embryonic heart. J Cell Biol 135:215–225
Salamon T (1963) Über eine familie mit recessiver Kraushaarigkeit, hypotrichose und anderen anomalien. Hautarzt 14:540–544.
Salomon D, Masgrau E, Vischer S et al (1994) Topography of mammalian connexins in human skin. J Invest Dermatol 103:240–247
Schaffer JV, Bazzi H, Vitebsky A et al (2006) Mutations in the desmoglein 4 gene underlie localized autosomal recessive hypotrichosis with monilethrix hairs and congenital scalp erosions. J Invest Dermatol 126:1286–1291
Schlake T, Schorpp M, Maul-Pavicic A et al (2000) Forkhead/winged-helix transcription factor Whn regulates hair keratin gene expression: molecular analysis of the nude skin phenotype. Dev Dyn 217:368–376
Schmidt A, Langbein L, Rode M et al (1997) Plakophilins 1a and 1b: widespread nuclear proteins recruited in specific epithelial cells as desmosomal plaque components. Cell Tissue Res 290:481–499
Schmidt-Ullrich R, Paus R (2005) Molecular principles of hair follicle induction and morphogenesis. BioEssays 27:247–261
Schmidt-Ullrich R, Tobin DJ, Lenhard D et al (2006) NF-kappaB transmits Eda A1/EdaR signalling to activate Shh and cyclin D1 expression, and controls post-initiation hair placode down growth. Development 133:1045–1057
Schorpp M, Hofmann M, Dear TN et al (1997) Characterization of mouse and human nude genes. Immunogenetics 46:509–515
Schweizer J, Bowden PE, Coulombe PA et al (2006) New consensus nomenclature for mammalian keratins. J Cell Biol 174:169–174
Serre G, Mils V, Haftek M et al (1991) Identification of late differentiation antigens of human cornified epithelia, expressed in re-organized desmosomes and bound to cross-linked envelope. J Invest Dermatol 97:1061–1072
Shen Z, Belinson J, Morton RE et al (1998) Phorbol 12-myristate 13-acetate stimulates lysophosphatidic acid secretion from ovarian and cervical cancer cells but not from breast or leukemia cells. Gynecol Oncol 71:364–368
Shimomura Y, Sakamoto F, Kariya N et al (2006) Mutations in the desmoglein 4 gene are associated with monilethrix-like congenital hypotrichosis. J Invest Dermatol 126:1281–1285
Shimomura Y, Wajid M, Shapiro L et al (2008) P-cadherin is a p63 target gene with a crucial role in the developing human limb bud and hair follicle. Development 135:743–753.
Shimomura Y, Wajid M, Ishii Y et al (2008) Disruption of P2RY5, an orphan G protein-coupled receptor, underlies autosomal recessive woolly hair. Nat Genet 40:335–339.
Simon M, Bernard D, Minondo AM et al (2001) Persistence of both peripheral and non-peripheral corneodesmosomes in the upper stratum corneum of winter xerosis skin versus only peripheral in normal skin. J Invest Dermatol 116:23–30
Simon M, Jonca N, Guerrin M et al (2001) Refined characterization of corneodesmosin proteolysis during terminal differentiation of human epidermis and its relationship to desquamation. J Biol Chem 276:20292–20299
Skorija K, Cox M, Sisk JM et al (2005) Ligand-independent actions of the vitamin D receptor maintain hair follicle homeostasis. Mol Endocrinol 19:855–862
Smith EA, Fuchs E (1998) Defining the interactions between intermediate filaments and desmosomes. J Cell Biol 141:1229–1241
Smith FJ, Morley SM, McLean WH (2002) A novel connexin 30 mutation in Clouston syndrome. J Invest Dermatol 118:530–532
Sonoda H, Aoki J, Hiramatsu T et al (2002) A novel phosphatidic acid-selective phospholipase A1 that produces lysophosphatidic acid. J Biol Chem 277:34254–34263
South AP (2004) Plakophilin 1: an important stabilizer of desmosomes. Clin Exp Dermatol 29:161–167
South AP, Wan H, Stone MG et al (2003) Lack of plakophilin 1 increases keratinocyte migration and reduces desmosome stability. J Cell Sci 116:3303–3314
Sprecher E, Bergman R, Richard G et al (2001) Hypotrichosis with juvenile macular dystrophy is caused by a mutation in CDH3, encoding P-cadherin. Nat Genet 29:134–136
Srivastava AK, Pispa J, Hartung AJ et al (1997) The Tabby phenotype is caused by mutation in a mouse homologue of the EDA gene that reveals novel mouse and human exons and encodes a protein (ectodysplasin-A) with collagenous domains. Proc Natl Acad Sci USA 94:13069–13074
Srivastava AK, Durmowicz MC, Hartung AJ et al (2001) Ectodysplasin-A1 is sufficient to rescue both hair growth and sweat glands in Tabby mice. Hum Mol Genet 10:2973–2981
Sundberg JP, Boggess D, Bascom C et al (2000) Lanceolate hair-J (lahJ): a mouse model for human hair disorders. Exp Dermatol 9:206–218
Taylor G, Lehrer MS, Jensen PJ et al (2000) Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell 102:451–461
Teubner B, Michel V, Pesch J et al (2003) Connexin30 (Gjb6)-deficiency causes severe hearing impairment and lack of endocochlear potential. Hum Mol Genet 12:13–21
Teulière J, Faraldo MM, Shtutman M et al (2004) beta-catenin-dependent and -independent effects of DeltaN-plakoglobin on epidermal growth and differentiation. Mol Cell Biol 24:8649–8661
Thompson CC, Bottcher MC (1997) The product of a thyroid hormone-responsive gene interacts with thyroid hormone receptors. Proc Natl Acad Sci USA 94:8527–8532
Tumbar T, Guasch G, Greco V et al (2004) Defining the epithelial stem cell niche in skin. Science 303:359–363
van Steensel MA, Steijlen PM, Bladergroen RS et al (2004) A phenotype resembling the Clouston syndrome with deafness is associated with a novel missense GJB2 mutation. J Invest Dermatol 123:291–293
van Steensel MA, Steijlen PM, Bladergroen RS et al (2005) A missense mutation in the type II hair keratin hHb3 is associated with monilethrix. J Med Genet 42:e19
Vasioukhin V, Bowers E, Bauer C et al (2001) Desmoplakin is essential in epidermal sheet formation. Nat Cell Biol 3:1076–1085
Wen XY, Bryce DM, Breitman ML (1998) Characterization of lpd (lipid defect): a novel mutation on mouse chromosome 16 associated with a defect in triglyceride metabolism. Hum Mol Genet 7:743–750
Wen XY, Hegele RA, Wang J et al (2003) Identification of a novel lipase gene mutated in lpd mice with hypertriglyceridemia and associated with dyslipidemia in humans. Hum Mol Genet 12:1131–1143
Whittock NV (2003) Genomic sequence analysis of the mouse desmoglein cluster reveals evidence for six distinct genes: characterization of mouse DSG4, DSG5, and DSG6. J Invest Dermatol 120:970–980
Whittock NV, Ashton GH, Dopping-Hepenstal PJ et al (1999) Striate palmoplantar keratoderma resulting from desmoplakin haploinsufficiency. J Invest Dermatol 113:940–946
Whittock NV, Wan H, Morley SM et al (2002) Compound heterozygosity for non-sense and mis-sense mutations in desmoplakin underlies skin fragility/woolly hair syndrome. J Invest Dermatol 118:232–238
Winter H, Rogers MA, Langbein L et al (1997) Mutations in the hair cortex keratin hHb6 cause the inherited hair disease monilethrix. Nat Genet 16:372–374
Wu H, Stanley JR, Cotsarelis G (2003) Desmoglein isotype expression in the hair follicle and its cysts correlates with type of keratinization and degree of differentiation. J Invest Dermatol 120:1052–1057
Xie Z, Chang S, Oda Y et al (2006) Hairless suppresses vitamin D receptor transactivation in human keratinocytes. Endocrinology 147:314–323
Yamasaki H (1991) Aberrant expression and function of gap junctions during carcinogenesis. Environ Health Perspect 93:191–197
Yang A, Kaghad M, Wang Y et al (1998) p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell 2:305–316.
Yang A, Schweitzer R, Sun D et al (1999) p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature 398:714–718.
Yin T, Green KJ (2004) Regulation of desmosome assembly and adhesion. Semin Cell Dev Biol 15:665–677
Yin T, Getsios S, Caldelari R et al (2005) Mechanisms of plakoglobin-dependent adhesion: desmosome-specific functions in assembly and regulation by epidermal growth factor receptor. J Biol Chem 280:40355–40363
Zlotogorski A, Hochberg Z, Mirmirani P et al (2003) Clinical and pathologic correlations in genetically distinct forms of atrichia. Arch Dermatol 139:1591–1596
Zlotogorski A, Marek D, Horev L et al (2006) An autosomal recessive form of monilethrix is caused by mutations in DSG4: clinical overlap with localized autosomal recessive hypotrichosis. J Invest Dermatol 126:1292–1296
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Shimomura, Y., Zlotogorski, A., Christiano, A. (2008). Molecular Genetics of Human Hair Diseases. In: Blume-Peytavi, U., Tosti, A., Trüeb, R. (eds) Hair Growth and Disorders. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-46911-7_6
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DOI: https://doi.org/10.1007/978-3-540-46911-7_6
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