Genomes and Genes
Gene Symbol: Krt8
Description: keratin 8
Alias: AA960620, AL022697, AU019895, Card2, EndoA, Krt-2.8, Krt2-8, keratin, type II cytoskeletal 8, CK-8, cytokeratin endo A, cytokeratin-8, keratin complex 2, basic, gene 8, type-II keratin Kb8
- Liu B, Liu Y, Du Y, Mardaryev A, Yang W, Chen H, et al. Cbx4 regulates the proliferation of thymic epithelial cells and thymus function. Development. 2013;140:780-8 pubmed publisher..Together, these data establish Cbx4 as a crucial regulator for the generation and maintenance of the thymic epithelium and, hence, for thymocyte development...
- Liu H, Ermilov A, Grachtchouk M, Li L, Gumucio D, Dlugosz A, et al. Multiple Shh signaling centers participate in fungiform papilla and taste bud formation and maintenance. Dev Biol. 2013;382:82-97 pubmed publisher..Shh signaling has roles in forming and maintaining fungiform papillae and taste buds, most likely via stage-specific autocrine and/or paracrine mechanisms, and by engaging epithelial/mesenchymal interactions. ..
- Driskell I, Oda H, Blanco S, Nascimento E, Humphreys P, Frye M. The histone methyltransferase Setd8 acts in concert with c-Myc and is required to maintain skin. EMBO J. 2012;31:616-29 pubmed publisher..Both overexpression of p63 and deletion of p53 rescue Setd8-induced apoptosis. Thus, Setd8 is a crucial inhibitor of apoptosis in skin and its activity is essential for epidermal stem cell survival, proliferation and differentiation. ..
- Toivola D, Omary M, Ku N, Peltola O, Baribault H, Eriksson J. Protein phosphatase inhibition in normal and keratin 8/18 assembly-incompetent mouse strains supports a functional role of keratin intermediate filaments in preserving hepatocyte integrity. Hepatology. 1998;28:116-28 pubmed..The absence or occurrence of defective K8/K18 filaments render animals more prone to liver damage, which supports the previously suggested roles of keratin IFs in maintenance of structural integrity. ..
- Baribault H, Price J, Miyai K, Oshima R. Mid-gestational lethality in mice lacking keratin 8. Genes Dev. 1993;7:1191-202 pubmed..This phenotype in mice differs from the reported function of simple epithelium keratins in Xenopus at the gastrulation stage. In mice, mK8 fulfills a vital function at 12 days postcoitum. ..
- Lu H, Hesse M, Peters B, Magin T. Type II keratins precede type I keratins during early embryonic development. Eur J Cell Biol. 2005;84:709-18 pubmed..Whether the premature expression of type II keratins relates to their proposed role in TNF- and Fas-mediated signalling is presently unknown. ..
- Nozaki M, Murata K, Morita T, Matsushiro A. Isolation of endo A cDNA from mouse 8-cell stage embryos. Biochem Biophys Res Commun. 1988;154:890-4 pubmed..Sequencing data of these clones showed that endo A mRNA present in the 8-cell stage embryo is identical to that of parietal yolk sac endoderm cells. ..
- Morrison K, Miesegaes G, Lumpkin E, Maricich S. Mammalian Merkel cells are descended from the epidermal lineage. Dev Biol. 2009;336:76-83 pubmed publisher..Thus, mammalian Merkel cells are derived from the skin lineage. ..
- Gilbert S, Loranger A, Marceau N. Keratins modulate c-Flip/extracellular signal-regulated kinase 1 and 2 antiapoptotic signaling in simple epithelial cells. Mol Cell Biol. 2004;24:7072-81 pubmed..This points to a new regulatory role of simple epithelium keratins in the c-Flip/ERK1/2 antiapoptotic signaling pathway. ..
- Toivola D, Nieminen M, Hesse M, He T, Baribault H, Magin T, et al. Disturbances in hepatic cell-cycle regulation in mice with assembly-deficient keratins 8/18. Hepatology. 2001;34:1174-83 pubmed..These effects could stem from disturbed functions of K8/18-dependent cell-cycle regulators, such as the signaling integrator, 14-3-3. ..
- Grimm S, Bu W, Longley M, Roop D, Li Y, Rosen J. Keratin 6 is not essential for mammary gland development. Breast Cancer Res. 2006;8:R29 pubmed..There was also increased co-localization of PR and bromodeoxyuridine, suggesting alterations in patterning events important for normal lobuloalveolar development. ..
- Toivola D, Krishnan S, Binder H, Singh S, Omary M. Keratins modulate colonocyte electrolyte transport via protein mistargeting. J Cell Biol. 2004;164:911-21 pubmed..Therefore, colonic keratins have a novel function in regulating electrolyte transport, likely by targeting ion transporters to their cellular compartments. ..
- Huang T, Krimm R. BDNF and NT4 play interchangeable roles in gustatory development. Dev Biol. 2014;386:308-20 pubmed publisher..Spatial and temporal differences in BDNF and NT4 expression can regulate differential gene expression in vivo and determine their specific roles during development. ..
- Ku N, Omary M. A disease- and phosphorylation-related nonmechanical function for keratin 8. J Cell Biol. 2006;174:115-25 pubmed
- Baribault H, Oshima R. Polarized and functional epithelia can form after the targeted inactivation of both mouse keratin 8 alleles. J Cell Biol. 1991;115:1675-84 pubmed..Our data show that mK8 is not required for simple epithelium formation of extraembryonic endoderm. ..
- Liu C, Saito F, Liu Z, Lei Y, Uehara S, Love P, et al. Coordination between CCR7- and CCR9-mediated chemokine signals in prevascular fetal thymus colonization. Blood. 2006;108:2531-9 pubmed..These results indicate coordination between Gcm2-dependent parathyroid and Foxn1-dependent thymic primordia in establishing CCL21/CCR7- and CCL25/CCR9-mediated chemokine guidance essential for prevascular fetal thymus colonization. ..
- DeMonte L, Porcellini S, Tafi E, Sheridan J, Gordon J, Depreter M, et al. EVA regulates thymic stromal organisation and early thymocyte development. Biochem Biophys Res Commun. 2007;356:334-40 pubmed..Collectively, these data suggest a role for EVA in structural organisation of the thymus and early lymphocyte development. ..
- Toivola D, Nakamichi I, Strnad P, Michie S, Ghori N, Harada M, et al. Keratin overexpression levels correlate with the extent of spontaneous pancreatic injury. Am J Pathol. 2008;172:882-92 pubmed publisher..Keratin absence or mutation is well tolerated after pancreatic but not liver injury, whereas excessive overexpression is toxic to the pancreas but not the liver when induced under basal conditions. ..
- Van Keymeulen A, Mascre G, Youseff K, Harel I, Michaux C, De Geest N, et al. Epidermal progenitors give rise to Merkel cells during embryonic development and adult homeostasis. J Cell Biol. 2009;187:91-100 pubmed publisher..Our study demonstrates that MCs arise from the epidermis by an Atoh1-dependent mechanism and opens new avenues for study of MC functions in sensory perception, neuroendocrine signaling, and MC carcinoma. ..
- Vijayaraj P, Kröger C, Reuter U, Windoffer R, Leube R, Magin T. Keratins regulate protein biosynthesis through localization of GLUT1 and -3 upstream of AMP kinase and Raptor. J Cell Biol. 2009;187:175-84 pubmed publisher..Our findings demonstrate a novel keratin function upstream of mTOR signaling via GLUT localization and have implications for pathomechanisms and therapy approaches for keratin disorders and the analysis of other gene families. ..
- Habtezion A, Toivola D, Asghar M, Kronmal G, Brooks J, Butcher E, et al. Absence of keratin 8 confers a paradoxical microflora-dependent resistance to apoptosis in the colon. Proc Natl Acad Sci U S A. 2011;108:1445-50 pubmed publisher..Therefore, unlike the proapoptotic effect of K8 mutation or absence in hepatocytes, lack of K8 confers resistance to colonocyte apoptosis in a microflora-dependent manner. ..
- Loranger A, Duclos S, Grenier A, Price J, Wilson Heiner M, Baribault H, et al. Simple epithelium keratins are required for maintenance of hepatocyte integrity. Am J Pathol. 1997;151:1673-83 pubmed..Taken together, these findings demonstrate that simple epithelium keratins are essential for the maintenance of hepatocyte structural and functional integrity. ..
- Zhou Q, Toivola D, Feng N, Greenberg H, Franke W, Omary M. Keratin 20 helps maintain intermediate filament organization in intestinal epithelia. Mol Biol Cell. 2003;14:2959-71 pubmed..Our data suggest the presence of unique regulatory domains for pancreatic and gastric K20 expression and support a significant role for K20 in maintaining keratin filaments in intestinal epithelia. ..
- Jaquemar D, Kupriyanov S, Wankell M, Avis J, Benirschke K, Baribault H, et al. Keratin 8 protection of placental barrier function. J Cell Biol. 2003;161:749-56 pubmed..The keratin-dependent protection of trophoblast giant cells from a maternal TNF-dependent apoptotic challenge may be a key function of simple epithelial keratins. ..
- Caulin C, Ware C, Magin T, Oshima R. Keratin-dependent, epithelial resistance to tumor necrosis factor-induced apoptosis. J Cell Biol. 2000;149:17-22 pubmed
- Hesse M, Franz T, Tamai Y, Taketo M, Magin T. Targeted deletion of keratins 18 and 19 leads to trophoblast fragility and early embryonic lethality. EMBO J. 2000;19:5060-70 pubmed..Our data also offer a rationale to explore the involvement of keratin mutations in early abortions during human pregnancies. ..
- Tamai Y, Ishikawa T, Bösl M, Mori M, Nozaki M, Baribault H, et al. Cytokeratins 8 and 19 in the mouse placental development. J Cell Biol. 2000;151:563-72 pubmed..These results indicate that K19 and K8 cooperate in ensuring the normal development of placental tissues. ..
- Klug D, Carter C, Gimenez Conti I, Richie E. Cutting edge: thymocyte-independent and thymocyte-dependent phases of epithelial patterning in the fetal thymus. J Immunol. 2002;169:2842-5 pubmed..However, thymocyte-derived signals are required during late fetal stages for continued development and maintenance of TEC subsets in the neonate and adult. ..
- Akiyama T, Shimo Y, Yanai H, Qin J, Ohshima D, Maruyama Y, et al. The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance. Immunity. 2008;29:423-37 pubmed publisher..These results show that developmental-stage-dependent cooperation between RANK and CD40 promotes mTEC development, thereby establishing self-tolerance. ..
- Ripen A, Nitta T, Murata S, Tanaka K, Takahama Y. Ontogeny of thymic cortical epithelial cells expressing the thymoproteasome subunit ?5t. Eur J Immunol. 2011;41:1278-87 pubmed publisher..These results indicate that ?5t expression in cTECs is dependent on Foxn1 but independent of thymocyte crosstalk or thymic medulla formation. ..
- Patel A, Krimm R. Neurotrophin-4 regulates the survival of gustatory neurons earlier in development using a different mechanism than brain-derived neurotrophic factor. Dev Biol. 2012;365:50-60 pubmed publisher..Therefore, compared to BDNF, NT-4 plays distinct roles in gustatory development; differences include timing, source of neurotrophin, and mechanism of action. ..
- Maricich S, Wellnitz S, Nelson A, Lesniak D, Gerling G, Lumpkin E, et al. Merkel cells are essential for light-touch responses. Science. 2009;324:1580-2 pubmed publisher..Merkel cells are, therefore, required for the proper encoding of Merkel receptor responses, suggesting that these cells form an indispensible part of the somatosensory system. ..
- Baribault H, Penner J, Iozzo R, Wilson Heiner M. Colorectal hyperplasia and inflammation in keratin 8-deficient FVB/N mice. Genes Dev. 1994;8:2964-73 pubmed..More importantly, the increase in mK8-/- gut epithelial cell number, rather than cell disruption, contrasts with the known function of epidermal keratins in providing mechanical strength. ..
- Thirumangalathu S, HARLOW D, Driskell A, Krimm R, Barlow L. Fate mapping of mammalian embryonic taste bud progenitors. Development. 2009;136:1519-28 pubmed publisher..These studies further suggest that mammalian taste bud development is very distinct from that of other epithelial appendages. ..
- Gilbert S, Loranger A, Daigle N, Marceau N. Simple epithelium keratins 8 and 18 provide resistance to Fas-mediated apoptosis. The protection occurs through a receptor-targeting modulation. J Cell Biol. 2001;154:763-73 pubmed..Together, the results strongly suggest that simple epithelium K8/K18 provide resistance to Fas-mediated apoptosis and that this protection occurs through a modulation of Fas targeting to the cell surface. ..
- Gill J, Malin M, Hollander G, Boyd R. Generation of a complete thymic microenvironment by MTS24(+) thymic epithelial cells. Nat Immunol. 2002;3:635-42 pubmed..These cells contained epithelial progenitor cells that were competent and sufficient to fully reconstitute the complex thymic epithelial microenvironment that supported normal T cell development. ..
- Vasseur M, Duprey P, Brulet P, Jacob F. One gene and one pseudogene for the cytokeratin endo A. Proc Natl Acad Sci U S A. 1985;82:1155-9 pubmed..6-kilobase pseudogene devoid of introns. A repetitive sequence belonging to the B2 family is located in the third intron of the gene. We have observed that transcription of B2 sequences and of the endo A gene are mutually exclusive. ..
- Kulesh D, Cecena G, Darmon Y, Vasseur M, Oshima R. Posttranslational regulation of keratins: degradation of mouse and human keratins 18 and 8. Mol Cell Biol. 1989;9:1553-65 pubmed..Therefore, cells that normally express keratins contain a proteolytic system similar to that found in experimentally manipulated fibroblasts which degrades keratin proteins not found in their normal polymerized state. ..
- Tamai Y, Takemoto Y, Matsumoto M, Morita T, Matsushiro A, Nozaki M. Sequence of EndoA gene encoding mouse cytokeratin and its methylation state in the CpG-rich region. Gene. 1991;104:169-76 pubmedA genomic clone obtained from mouse liver DNA using a mouse cytokeratin EndoA cDNA probe revealed the complete sequence of the EndoA gene...
- Mbiene J, Roberts J. Distribution of keratin 8-containing cell clusters in mouse embryonic tongue: evidence for a prepattern for taste bud development. J Comp Neurol. 2003;457:111-22 pubmed..dorsal surface at 13 days of gestation, we observed embryonic taste bud primordia as discrete collections of cytokeratin 8-positive and elongated cells in epithelial placodes in the anterior tongue...
- Blij S, Frum T, Akyol A, Fearon E, Ralston A. Maternal Cdx2 is dispensable for mouse development. Development. 2012;139:3969-72 pubmed publisher..Here, we genetically ablated maternal Cdx2 using a Cre/lox strategy, and we definitively establish that maternal Cdx2 is not essential for mouse development. ..
- Li L, Liu C, Biechele S, Zhu Q, Song L, Lanner F, et al. Location of transient ectodermal progenitor potential in mouse development. Development. 2013;140:4533-43 pubmed publisher..Our work not only improves our understanding of ectodermal layer development in early embryos, but also provides a framework for regenerative differentiation towards ectodermal tissues. ..
- Zheng Q, Hursting S, Reizes O. Leptin regulates cyclin D1 in luminal epithelial cells of mouse MMTV-Wnt-1 mammary tumors. J Cancer Res Clin Oncol. 2012;138:1607-12 pubmed publisher..Thus, leptin therapeutics may inhibit breast cancer via distinct mechanisms related to tumor type. ..
- Mori M, Mahoney J, Stupnikov M, Paez Cortez J, Szymaniak A, Varelas X, et al. Notch3-Jagged signaling controls the pool of undifferentiated airway progenitors. Development. 2015;142:258-67 pubmed publisher..Analysis of human lungs showing similar abnormalities and decreased NOTCH3 expression in subjects with chronic obstructive pulmonary disease suggests an involvement of NOTCH3-dependent events in the pathogenesis of this condition. ..
- Misiorek J, Lähdeniemi I, Nyström J, Paramonov V, Gullmets J, Saarento H, et al. Keratin 8-deletion induced colitis predisposes to murine colorectal cancer enforced by the inflammasome and IL-22 pathway. Carcinogenesis. 2016;37:777-786 pubmed publisher..The K8-null mouse models also provide novel epithelial-derived robust colon-specific CRC models. ..
- Giroux S, Charron J. Defective development of the embryonic liver in N-myc-deficient mice. Dev Biol. 1998;195:16-28 pubmed
- Sugiyama Y, Takabe Y, Nakakura T, Tanaka S, Koike T, Shiojiri N. Sinusoid development and morphogenesis may be stimulated by VEGF-Flk-1 signaling during fetal mouse liver development. Dev Dyn. 2010;239:386-97 pubmed publisher..Therefore, VEGF-Flk-1 signaling may play an important role in the growth and morphogenesis of primitive sinusoids during fetal liver development. ..
- Nitou M, Ishikawa K, Shiojiri N. Immunohistochemical analysis of development of desmin-positive hepatic stellate cells in mouse liver. J Anat. 2000;197 Pt 4:635-46 pubmed..These developmental changes in the geography of desmin-positive cells in the liver parenchyma and their morphology may be associated with their maturation and interactions with other cell types. ..
- Adachi K, Soeta Saneyoshi C, Sagara H, Iwakura Y. Crucial role of Bysl in mammalian preimplantation development as an integral factor for 40S ribosome biogenesis. Mol Cell Biol. 2007;27:2202-14 pubmed..These findings provide evidence for a crucial role of Bysl as an integral factor for ribosome biogenesis and suggest a critical dependence of blastocyst formation on active translation machinery. ..
- Mahoney Z, Sammut B, Xavier R, Cunningham J, Go G, Brim K, et al. Discs-large homolog 1 regulates smooth muscle orientation in the mouse ureter. Proc Natl Acad Sci U S A. 2006;103:19872-7 pubmed..Our results suggest that (i) besides its well documented role in regulating epithelial polarity, Dlgh1 also regulates smooth muscle orientation, and (ii) human DLG1 mutations may contribute to hereditary forms of hydronephrosis. ..
- Kan N, Stemmler M, Junghans D, Kanzler B, de Vries W, Dominis M, et al. Gene replacement reveals a specific role for E-cadherin in the formation of a functional trophectoderm. Development. 2007;134:31-41 pubmed..Thus, N-cadherin can maintain epithelia in differentiating ES cells, but not during the formation of the trophectoderm. Our results point to a specific and unique function for E-cadherin during mouse preimplantation development. ..
- Elling U, Klasen C, Eisenberger T, Anlag K, Treier M. Murine inner cell mass-derived lineages depend on Sall4 function. Proc Natl Acad Sci U S A. 2006;103:16319-24 pubmed..These data establish Sall4 as an essential transcription factor required for the early development of inner cell mass-derived cell lineages. ..
- Cui X, Li X, Shen X, Bae Y, Kang J, Kim N. Transcription profile in mouse four-cell, morula, and blastocyst: Genes implicated in compaction and blastocoel formation. Mol Reprod Dev. 2007;74:133-43 pubmed..The identification of the genes being expressed in here will provide insight into the complex gene regulatory networks effecting compaction and blastocoel formation...
- Le Henaff C, Faria Da Cunha M, Hatton A, Tondelier D, Marty C, Collet C, et al. Genetic deletion of keratin 8 corrects the altered bone formation and osteopenia in a mouse model of cystic fibrosis. Hum Mol Genet. 2016;25:1281-93 pubmed publisher..Here we report a key role for the intermediate filament protein keratin 8 (Krt8), in the osteoblast dysfunctions in F508del-Cftr mice...
- Ursitti J, Lee P, Resneck W, McNally M, Bowman A, O Neill A, et al. Cloning and characterization of cytokeratins 8 and 19 in adult rat striated muscle. Interaction with the dystrophin glycoprotein complex. J Biol Chem. 2004;279:41830-8 pubmed..Together these results indicate that at least two cytokeratins are expressed in adult striated muscle, where they may contribute to the organization of both the myoplasm and sarcolemma. ..
- Pignon J, Grisanzio C, Geng Y, Song J, Shivdasani R, Signoretti S. p63-expressing cells are the stem cells of developing prostate, bladder, and colorectal epithelia. Proc Natl Acad Sci U S A. 2013;110:8105-10 pubmed publisher..Because p63 is a master regulator of stratified epithelial development, this finding provides a unique developmental insight into the cell of origin of squamous cell metaplasia and squamous cell carcinoma of the colon. ..
- Ain R, Trinh M, Soares M. Interleukin-11 signaling is required for the differentiation of natural killer cells at the maternal-fetal interface. Dev Dyn. 2004;231:700-8 pubmed..Thus, the defect in NK precursor cell maturation was not intrinsic to the NK precursor cells but was dependent upon the tissue environment. In summary, IL-11 signaling is required for decidual-specific maturation of NK cells. ..