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New facets of keratin K77: interspecies variations of expression and different intracellular location in embryonic and adult skin of humans and mice

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Abstract

The differential expression of keratins is central to the formation of various epithelia and their appendages. Structurally, the type II keratin K77 is closely related to K1, the prototypical type II keratin of the suprabasal epidermis. Here, we perform a developmental study on K77 expression in human and murine skin. In both species, K77 is expressed in the suprabasal fetal epidermis. While K77 appears after K1 in the human epidermis, the opposite is true for the murine tissue. This species-specific pattern of expression is also found in conventional and organotypic cultures of human and murine keratinocytes. Ultrastructure investigation shows that, in contrast to K77 intermediate filaments of mice, those of the human ortholog are not attached to desmosomes. After birth, K77 disappears without deleterious consequences from human epidermis while it is maintained in the adult mouse epidermis, where its presence has so far gone unnoticed. After targeted Krt1 gene deletion in mice, K77 is normally expressed but fails to functionally replace K1. Besides the epidermis, both human and mouse K77 are present in luminal duct cells of eccrine sweat glands. The demonstration of a K77 ortholog in platypus but not in non-mammalian vertebrates identifies K77 as an evolutionarily ancient component of the mammalian integument that has evolved different patterns of intracellular distribution and adult tissue expression in primates.

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References

  • Bader BL, Jahn L, Franke WW (1988) Low level expression of cytokeratins 8, 18 and 19 in vascular smooth muscle cells of human umbilical cord and in cultured cells derived therefrom, with an analysis of the chromosomal locus containing the cytokeratin 19 gene. Eur J Cell Biol 47:300–319

    PubMed  CAS  Google Scholar 

  • Bazzi H, Fantauzzo KA, Richardson GD, Jahoda CAB, Christiano AM (2007) Transcriptional profiling of developing mouse epidermis reveals novel patterns of coordinated gene expression. Dev Dyn 236:961–979

    Article  PubMed  CAS  Google Scholar 

  • Boehnke K, Mirancea N, Pavesio A, Fusenig NE, Boukamp P, Stark HJ (2007) Effects of fibroblasts and microenvironment on epidermal regeneration and tissue function in long-term skin equivalents. Eur J Cell Biol 86:731–746

    Article  PubMed  CAS  Google Scholar 

  • Boukamp P, Petrussevska RT, Breitkreutz D, Hornung J, Markham A, Fusenig NE (1988) Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J Cell Biol 106:761–771

    Article  PubMed  CAS  Google Scholar 

  • Byrne C, Hardman M, Nield K (2003) Covering the limb–formation of the integument. J Anat 202:113–123

    Article  PubMed  Google Scholar 

  • Candi E, Tarcsa E, Digiovanna JJ, Compton JG, Elias PM, Marekov LN, Steinert PM (1998) A highly conserved lysine residue on the head domain of type II keratins is essential for the attachment of keratin intermediate filaments to the cornified cell envelope through isopeptide crosslinking by transglutaminases. Proc Natl Acad Sci USA 95:2067–2072

    Article  PubMed  CAS  Google Scholar 

  • Candi E, Schmidt R, Melino G (2005) The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol 6:328–340

    Article  PubMed  CAS  Google Scholar 

  • Coulombe PA, Kopan R, Fuchs E (1989) Expression of keratin K14 in the epidermis and hair follicle. Insights into complex programs of differentiation. J Cell Biol 109:2295–2312

    Article  PubMed  CAS  Google Scholar 

  • Cui CY, Childress V, Piao Y, Michel M, Johnson AA, Kunisada M, Ko MS, Kaestner KH, Marmorstein AD, Schlessinger D (2012) Forkhead transcription factor FoxA1 regulates sweat secretion through Bestrophin 2 anion channel and Na-K-Cl cotransporter 1. Proc Natl Acad Soc USA 109:1199–1203

    Article  CAS  Google Scholar 

  • Durchdewald M, Beyer TA, Johnson DA, Johnson JA, Werner S, Auf dem Keller U (2007) Electrophilic chemicals but not UV irradiation or reactive oxygen species activate Nrf2 in keratinocytes in vitro and in vivo. J Invest Dermatol 127:646–653

    Article  PubMed  CAS  Google Scholar 

  • Eckhart L, Ballaun C, Hermann M, Vandeberg JL, Sipos W, Uthman A, Fischer H, Tschachler E (2008) Identification of novel mammalian caspases reveals an important role of gene loss in shaping the human caspase repertoire. Mol Biol Evol 25:831–841

    Google Scholar 

  • Gkegkes ID, Aroni K, Agrogiannis G, Patsouris ES, Konstandinidou AE (2013) Expression of caspase-14 and keratin K19 in the human epidermis and appendages during fetal skin development. Arch Dermatol Res 305:379–397

    Article  PubMed  CAS  Google Scholar 

  • Groscurth P (2002) Anatomy of sweat glands. Curr Probl Dermatol 30:1–9

    Article  PubMed  Google Scholar 

  • Hashimoto K, Gross BG, Lever WF (1966) The ultrastructure of human embryo skin II. The formation of intradermal portion of the eccrine sweat duct and of the secretory segment during the first half of embryonic life. J Invest Dermatol 46:513–529

    Google Scholar 

  • Hesse M, Zimek A, Weber K, Magin TM (2004) Comprehensive analysis of keratin gene clusters in humans and rodents. Eur J Cell Biol 83:19–26

    Article  PubMed  CAS  Google Scholar 

  • Heynold H (1874) Über die Knäueldrüsen des Menschen. Arch pathol Anat Physiol Klin Med 61:77–90

    Google Scholar 

  • Holbrook K (2006) Embryogenesis of the skin. In: Irvine AD, Hoeger PH, Yan AC (eds) Harper’s Textbook of pediatric Dermatology, 2nd edn. Blackwell, Oxford , pp 21–241

  • Holbrook KA, Odland GF (1975) The fine structure of developing human epidermis: light, scanning, and transmission electron microscopy of the periderm. J Invest Dermatol 65:16–38

    Article  PubMed  CAS  Google Scholar 

  • Icre G, Wahli W, Michalik L (2006) Functions of the peroxisome proliferator-activated receptor (PPAR) α and β in skin homeostasis, epithelial repair, and morphogenesis. J Invest Dermatol 11:30–35

    Article  CAS  Google Scholar 

  • Jackson BW, Grund C, Schmid E, Bürki K, Franke WW, Illmensee K (1980) Formation of cytoskeletal elements during mouse embryogenesis Intermediate filaments of the cytokeratin type and desmosomes in preimplantation embryos. Differentiation 17:161–179

    Article  PubMed  CAS  Google Scholar 

  • Jave-Suarez LF, Langbein L, Winter H, Schweizer J (2004) Androgen regulation of the human hair follicle: the type I hair keratin hHa7 is a direct target gene in trichocytes. J Invest Dermatol 122:555–564

    Article  PubMed  CAS  Google Scholar 

  • Kimonis V, DiGiovanna JJ, Yang JM, Doyle SZ, Bale SJ, Compton JG (1994) A mutation in the V1 end domain of keratin 1 in non-epidermolytic palmar-plantar Keratoderma. J Invest Dermatol 103:764–769

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Kunisada M, Cui CY, Piao Y, Minoru SH, Schlessinger D (2009) Requirement for Shh and Fox family genes at different stages in sweat gland development. Hum Mol Genet 18:1769–1778

    Article  PubMed  CAS  Google Scholar 

  • Langbein L, Schweizer J (2005) The keratins of the human hair follicle. Internat Rev Cytol 243:1–78

    Article  CAS  Google Scholar 

  • Langbein L, Schweizer J (2013) The keratins of the human hair follicle In: Camacho FM, Tosti A, Price VH, Randall VA, (Eds) Montagna Tricología Enfermedades del folículo pilosebáceo Madrid: Editorial Aula Medica Ed, pp 73–108

  • Langbein L, Heid HW, Moll I, Franke WW (1993) Molecular characterization of the body site-specific human cytokeratin 9 - cDNA cloning, amino acid sequence and tissue specificity of gene expression. Differentiation 55:57–73

    Article  PubMed  CAS  Google Scholar 

  • Langbein L, Rogers MA, Praetzel S, Winter H, Schweizer J (2003) K6irs1, K6irs3 and K6irs4 represent the inner root sheath-specific type II epithelial keratins in the human hair follicle. J Invest Dermatol 120:512–522

    Article  PubMed  CAS  Google Scholar 

  • Langbein L, Spring H, Rogers MA, Praetzel S, Schweizer J (2004) Hair keratins and hair follicle-specific epithelial keratins. Meth Cell Biol 78:413–451

    Article  CAS  Google Scholar 

  • Langbein L, Rogers MA, Praetzel S, Cribier B, Peltre B, Gassler N, Schweizer J (2005) Characterization of a novel human type II epithelial keratin K1b, specifically expressed in eccrine sweat glands. J Invest Dermatol 125:428–444

    Article  PubMed  CAS  Google Scholar 

  • Langbein L, Rogers MA, Praetzel-Wunder S, Helmke B, Schirmacher P, Schweizer J (2006) K25 (K25irs1), K26 (K25irs2), K27 (K25irs3) and K28 (K25irs4) represent the type I inner root sheath (IRS) keratins of the human hair follicle. J Invest Dermatol 126:2377–2386

    Article  PubMed  CAS  Google Scholar 

  • Langbein L, Rogers MA, Praetzel-Wunder S, Boeckler D, Schirmacher P, Schweizer J (2007) The novel keratins K39 and K40 are the latest expressed type II hair keratins and complete the human hair keratin family. J Invest Dermatol 127:1532–1535

    Article  PubMed  CAS  Google Scholar 

  • Langbein L, Eckhart L, Rogers MA, Praetzel-Wunder S, Schweizer J (2010a) Against the rules: human keratin K80 Two functional alternative splice variants, K80 and K80.1, with special cellular localization in a wide range of epithelia. J Biol Chem 285:36909–36921

    Article  PubMed  CAS  Google Scholar 

  • Langbein L, Yoshida H, Praetzel-Wunder S, Parry DAD, Schweizer J (2010b) The keratins of the human hair medulla: the riddle in the middle. J Invest Dermatol 130:55–73

    Article  PubMed  CAS  Google Scholar 

  • Lee SC, Lee JB, Kook JP, Seo JJ, Nam KI, Park SS, Kim YP (1999) Expression of differentiation markers during fetal skin development in humans: Immunohistochemical studies on the precursor proteins forming the cornified envelope. J Invest Dermatol 12:882–886

    Article  Google Scholar 

  • McGowan KM, Coulombe P (1998) Onset of keratin 17 expression coincides with the definition of major epithelial lineages during skin development. J Cell Biol 143:469–486

    Article  PubMed  CAS  Google Scholar 

  • Meng JJ, Bornslaeger EA, Green KJ, Steinert PM, Ip W (1997) Two-hybrid analysis reveals fundamental differences in direct interactions between desmoplakin and cell type-specific intermediate filaments. J Biol Chem 272:21495–21503

    Article  PubMed  CAS  Google Scholar 

  • Moll R, Moll I, Wiest W (1982) Changes in the pattern of cytokeratin polypeptides in epidermis and hair follicles during skin development in human fetuses. Differentiation 23:170–178

    Article  PubMed  CAS  Google Scholar 

  • Moll R, Divo M, Langbein L (2008) The human keratins: biology and pathology. Histochem Cell Biol 129:705–733

    Article  PubMed  CAS  Google Scholar 

  • Nakamura M, Tokura Y (2009) The localization of label-retaining cells in eccrine gland. J Invest Dermatol 129:2077–2078

    Article  PubMed  CAS  Google Scholar 

  • Paladini RD, Takahashi K, Bravo NS, Coulombe PA (1996) Onset of re-epithelialization after skin injury correlates with a reorganization of keratin filaments in wound edge keratinocytes: defining a potential role for keratin 16. J Cell Biol 132:381–397

    Article  PubMed  CAS  Google Scholar 

  • Reichelt J, Magin TM (2002) Hyperproliferation, induction of c-Myc and 14-3-3 sigma, but no cell fragility in keratin-10-null mice. J Cell Sci 115:2639–2650

    PubMed  CAS  Google Scholar 

  • Reichelt J, Büssow H, Grund C, Magin TM (2001) Formation of a normal epidermis supported by increased stability of keratins 5 and 14 in keratin 10 null mice. Mol Biol Cell 12:1557–1568

    Article  PubMed  CAS  Google Scholar 

  • Reichelt J, Breiden B, Sandhoff K, Magin TM (2004) Loss of keratin 10 is accompanied by increased sebocyte proliferation and differentiation. Eur J Cell Biol 83:747–759

    Article  PubMed  CAS  Google Scholar 

  • Riehl A (2009) Identification and characterization of gene regulatory networks controlled by the receptor RAGE in inflammation and cancer. PhD thesis, University of Heidelberg, Germany

  • Rogers MA, Winter H, Langbein L, Bleiler R, Schweizer J (2004) The human type I keratin gene family: characterization of new hair follicle specific members and evaluation of the chromosome 17q212 gene domain. Differentiation 72:527–540

    Article  PubMed  CAS  Google Scholar 

  • Rogers MA, Edler L, Winter H, Langbein L, Beckmann I, Schweizer J (2005) Characterization of new members of the human type II keratin gene family and a general evaluation of the keratin gene domain on chromosome 12q1313. J Invest Dermatol 124:536–544

    Article  PubMed  CAS  Google Scholar 

  • Roth W, Kumar V, Beer HD, Richter M, Wohlenberg C, Reuter U, Thiering S, Staratschek-Jox A, Hofmann A, Kreusch F, Schultze JL, Vogl T, Roth J, Reichelt J, Hausser I, Magin TM (2012) Keratin 1 maintains skin integrity and participates in an inflammatory network in skin through interleukin-18. J Cell Sci 125:5269–5279

    Article  PubMed  CAS  Google Scholar 

  • Rothnagel JA, Greenhalgh DA, Gagne TA, Longley MA, Roop DR (1993) Identification of a calcium-inducible, epidermal-specific regulatory element in the 3′-flanking region of the human keratin 1 gene. J Invest Dermatol 101:506–513

    Article  PubMed  CAS  Google Scholar 

  • Schweizer J, Bowden PE, Coulombe PA, Langbein L, Lane EB, Magin TM, Maltheis L, Omary MB, Parry DA, Rogers MA, Wright M (2006) A new consensus nomenclature for mammalian keratins. J Cell Biol 174:169–174

    Article  PubMed  CAS  Google Scholar 

  • Smith EA, Fuchs E (1998) Defining the interaction between intermediate filaments and desmosomes. J Cell Biol 141:1229–1241

    Article  PubMed  CAS  Google Scholar 

  • Stark HJ, Willhauck MJ, Mirancea N, Boehnke K, Nord I, Breitkreutz D, Pavesio A, Boukamp P, Fusenig NE (2004) Authentic fibroblast matrix in dermal equivalents normalises epidermal histogenesis and dermo-epidermal junction in organotypic co-culture. Eur J Cell Biol 83:631–645

    Article  PubMed  Google Scholar 

  • Stöhr P (1906) Lehrbuch der Histologie und der Mikroskopischen Anatomie des Menschen, 12th edn. G Fischer, Jena, pp 358–359

    Google Scholar 

  • Tao H, Cox DR, Frazer KA (2006) Allele-specific KRT1 expression is a complex trait. PLoS Genet 2:e93

    Article  PubMed  Google Scholar 

  • Tao H, Berno AJ, Cox DR, Frazer KA (2007) In vitro human keratinocyte migration rates are associated with SNPs in the KRT1 interval. PLoS ONE 2:e697

    Article  PubMed  Google Scholar 

  • Taylor DK, Bubier JA, Silva KA, Sundberg JP (2012) Development, structure, and keratin expression in C57BL/6J mouse eccrine glands. Vet Pathol 49:146–154

    Article  PubMed  CAS  Google Scholar 

  • Tintignac LA, Lagirand J, Batonnet S, Sirri V, Leibovitch MP, Leibovitch SA (2005) Degradation of MyoD mediated by the SCF (MAFbx) ubiquitin ligase. J Biol Chem 280:2847–2856

    Article  PubMed  CAS  Google Scholar 

  • Tokuyasu KT (1989) Use of poly(vinylpyrrolidone) and poly(vinyl alcohol) for cryo-ultramicrotomy. Histochem J 21:163–171

    Article  PubMed  CAS  Google Scholar 

  • Tokuyasu KT (1997) Immuno-cytochemistry on ultrathin cryosections. In: Spector DL, Goldman RD, Leinwand LA (eds) Cells, alaboratory manual, vol 3, Subcellular localization of genes and their products. Cold Spring Harbour Laboratory, Cold Spring Harbour, pp 1311–13127

  • Vandebergh W, Bossuyt F (2012) Recurrent functional divergence of early tetrapod keratins in amphibian toe pads and mammalian hair. Mol Biol Evol 29:995–1004

    Article  PubMed  CAS  Google Scholar 

  • Viallet JP, Dhouailly D (1994) Retinoic acid and mouse skin morphogenesis I. Expression pattern of retinoic acid receptor genes during hair vibrissa follicle, plantar, and nasal gland development. J Invest Dermatol 103:116–121

    Article  PubMed  CAS  Google Scholar 

  • Wallace L, Roberts-Thompson L, Reichelt J (2012) Deletion of K1/K10 does not impair epidermal stratification but affects desmosomal structure and nuclear integrity. J Cell Science 125:1750–1758

    Article  PubMed  CAS  Google Scholar 

  • Weiss RA, Eichner R, Sun TT (1984) Monoclonal antibody analysis of keratin expression in epidermal diseases: a 48- and 56-kdalton keratin as molecular markers for hyperproliferative keratinocytes. J Cell Biol 98:1397–1406

    Article  PubMed  CAS  Google Scholar 

  • Winter H, Langbein L, Praetzel S, Jacobs M, Rogers MA, Leigh IM, Tidman N, Schweizer J (1998) A novel human type II epithelial keratin, K6hf, specifically expressed in the companion layer of the hair follicle. J Invest Dermatol 111:955–962

    Article  PubMed  CAS  Google Scholar 

  • Winter H, Langbein L, Krawczak M, Cooper DN, Jave-Suarez LF, Rogers MA, Praetzel S, Heidt PJ, Schweizer J (2001) Human type I hair keratin pseudogene ΨhHaA has functional orthologs in the chimpanzee and gorilla: evidence for recent inactivation of the human gene after the Pan-Homo divergence. Hum Genet 108:37–42

    Article  PubMed  CAS  Google Scholar 

  • Wong P, Coulombe PA (2003) Loss of keratin 6 (K6) proteins reveals a function for intermediate filaments during wound repair. J Cell Biol 163:327–337

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This study was supported by the Wilhelm Sander-Stiftung, Munich (Grant 2007.133.2 to L.L.) and in parts by the Newcastle Health Care Charity and the Newcastle upon Tyne Hospitals NHS Charity (Grant PFC/ ML/0809 to J.R.). We thank Hans-Juergen Stark and Iris Martin for normal (NEHK) and immortal (HaCaT) human keratinocytes of adherent and organotypic cultures, Peter Angel for immortalized mouse keratinocytes, Peter Krieg and Sabine Rosenberger for mouse OTCs as well as Hermann Stammer for his support with qPCR and the Core Facility Electron Microscopy for technical equipment (all German Cancer Research Center, Heidelberg, Germany). We are grateful to Marianne Holtkoetter (Wilhelma, Stuttgart, Germany) for providing us with skin of a stillborn gorilla and Ingrid Hausser-Siller (EM-lab Dermatology and EM Core facility, Heidelberg University, Germany) for her invaluable support for our start in ultrathin cryo-sectioning as well as David A. Parry (Palmerston, New Zealand), Rudolf Leube (Aachen, Germany) and Ralf Paus (Luebeck, Germany) for fruitful discussions and Arunima Murgai (Newcastle, UK) for rectifying the English language.

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Authors and Affiliations

  1. Genetics of Skin Carcinogenesis, A110, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Lutz Langbein & Silke Praetzel-Wunder

  2. German Cancer Research Center, Heidelberg, Germany

    Walter Kittstein & Juergen Schweizer

  3. Institute of Cellular Medicine, Dermatological Sciences, Newcastle University, Newcastle upon Tyne, UK

    Julia Reichelt

  4. Department of Dermatology, Medical University of Vienna, Vienna, Austria

    Leopold Eckhart

  5. Institute of Pathology, RWTH Aachen University, Aachen, Germany

    Nikolaus Gassler

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  1. Lutz Langbein
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Correspondence to Lutz Langbein.

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Langbein, L., Reichelt, J., Eckhart, L. et al. New facets of keratin K77: interspecies variations of expression and different intracellular location in embryonic and adult skin of humans and mice. Cell Tissue Res 354, 793–812 (2013). https://doi.org/10.1007/s00441-013-1716-5

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