{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:20:07Z","timestamp":1787019607173,"version":"build-2736575974"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cell Biol"],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cutaneous wound repair in adult mammals does not regenerate the original epithelial architecture and results in altered skin function. We propose that lack of regeneration may be due to the absence of appropriate molecular signals to promote regeneration. In this study, we investigated the regulation of Wnt signaling during cutaneous wound healing and the consequence of activating either the beta-catenin-dependent or beta-catenin-independent Wnt signaling on epidermal architecture during wound repair.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We determined that the expression of Wnt ligands that typically signal via the beta-catenin-independent pathway is up-regulated in the wound while the beta-catenin-dependent Wnt signaling is activated in the hair follicles adjacent to the wound edge. Ectopic activation of beta-catenin-dependent Wnt signaling with lithium chloride in the wound resulted in epithelial cysts and occasional rudimentary hair follicle structures within the epidermis. In contrast, forced expression of Wnt-5a in the deeper wound induced changes in the interfollicular epithelium mimicking regeneration, including formation of epithelia-lined cysts in the wound dermis, rudimentary hair follicles and sebaceous glands, without formation of tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that adult interfollicular epithelium is capable of responding to Wnt morphogenic signals necessary for restoring epithelial tissue patterning in the skin during wound repair.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/1471-2121-7-4","type":"journal-article","created":{"date-parts":[[2006,1,23]],"date-time":"2006-01-23T07:46:16Z","timestamp":1138002376000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":124,"title":["Wnt signaling induces epithelial differentiation during cutaneous wound healing"],"prefix":"10.1186","volume":"7","author":[{"given":"Carrie","family":"Fathke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynne","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavita","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Hocking","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall","family":"Moon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Isik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2006,1,20]]},"reference":[{"issue":"5309","key":"177_CR1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1126\/science.276.5309.75","volume":"276","author":"P Martin","year":"1997","unstructured":"Martin P: Wound healing--aiming for perfect skin regeneration. Science. 1997, 276 (5309): 75-81. 10.1126\/science.276.5309.75.","journal-title":"Science"},{"issue":"5656","key":"177_CR2","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1126\/science.1092436","volume":"303","author":"T Tumbar","year":"2004","unstructured":"Tumbar T, Guasch G, Greco V, Blanpain C, Lowry WE, Rendl M, Fuchs E: Defining the epithelial stem cell niche in skin. Science. 2004, 303 (5656): 359-363. 10.1126\/science.1092436.","journal-title":"Science"},{"issue":"5","key":"177_CR3","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.cell.2004.08.012","volume":"118","author":"C Blanpain","year":"2004","unstructured":"Blanpain C, Lowry WE, Geoghegan A, Polak L, Fuchs E: Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell. 2004, 118 (5): 635-648. 10.1016\/j.cell.2004.08.012.","journal-title":"Cell"},{"issue":"12","key":"177_CR4","doi-asserted-by":"publisher","first-page":"4279","DOI":"10.1091\/mbc.E02-02-0105","volume":"13","author":"PA Zuk","year":"2002","unstructured":"Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH: Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002, 13 (12): 4279-4295. 10.1091\/mbc.E02-02-0105.","journal-title":"Mol Biol Cell"},{"issue":"5","key":"177_CR5","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1634\/stemcells.22-5-812","volume":"22","author":"C Fathke","year":"2004","unstructured":"Fathke C, Wilson L, Hutter J, Kapoor V, Smith A, Hocking A, Isik F: Contribution of bone marrow-derived cells to skin: collagen deposition and wound repair. Stem Cells. 2004, 22 (5): 812-822. 10.1634\/stemcells.22-5-812.","journal-title":"Stem Cells"},{"issue":"3","key":"177_CR6","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/S1534-5807(03)00266-1","volume":"5","author":"MT Veeman","year":"2003","unstructured":"Veeman MT, Axelrod JD, Moon RT: A second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling. Dev Cell. 2003, 5 (3): 367-377. 10.1016\/S1534-5807(03)00266-1.","journal-title":"Dev Cell"},{"issue":"7035","key":"177_CR7","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1038\/nature03319","volume":"434","author":"T Reya","year":"2005","unstructured":"Reya T, Clevers H: Wnt signalling in stem cells and cancer. Nature. 2005, 434 (7035): 843-850. 10.1038\/nature03319.","journal-title":"Nature"},{"issue":"5","key":"177_CR8","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/S0092-8674(00)81631-1","volume":"95","author":"U Gat","year":"1998","unstructured":"Gat U, DasGupta R, Degenstein L, Fuchs E: De Novo hair follicle morphogenesis and hair tumors in mice expressing a truncated beta-catenin in skin. Cell. 1998, 95 (5): 605-614. 10.1016\/S0092-8674(00)81631-1.","journal-title":"Cell"},{"issue":"3","key":"177_CR9","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1083\/jcb.148.3.567","volume":"148","author":"J Huelsken","year":"2000","unstructured":"Huelsken J, Vogel R, Brinkmann V, Erdmann B, Birchmeier C, Birchmeier W: Requirement for beta-catenin in anterior-posterior axis formation in mice. J Cell Biol. 2000, 148 (3): 567-578. 10.1083\/jcb.148.3.567.","journal-title":"J Cell Biol"},{"issue":"1-2","key":"177_CR10","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/S0925-4773(01)00452-X","volume":"107","author":"S Reddy","year":"2001","unstructured":"Reddy S, Andl T, Bagasra A, Lu MM, Epstein DJ, Morrisey EE, Millar SE: 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. 2001, 107 (1-2): 69-82. 10.1016\/S0925-4773(01)00452-X.","journal-title":"Mech Dev"},{"issue":"1","key":"177_CR11","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1006\/excr.1998.4152","volume":"243","author":"A Saitoh","year":"1998","unstructured":"Saitoh A, Hansen LA, Vogel JC, Udey MC: Characterization of Wnt gene expression in murine skin: possible involvement of epidermis-derived Wnt-4 in cutaneous epithelial- mesenchymal interactions. Exp Cell Res. 1998, 243 (1): 150-160. 10.1006\/excr.1998.4152.","journal-title":"Exp Cell Res"},{"issue":"20","key":"177_CR12","doi-asserted-by":"crossref","first-page":"4557","DOI":"10.1242\/dev.126.20.4557","volume":"126","author":"R DasGupta","year":"1999","unstructured":"DasGupta R, Fuchs E: Multiple roles for activated LEF\/TCF transcription complexes during hair follicle development and differentiation. Development. 1999, 126 (20): 4557-4568.","journal-title":"Development"},{"issue":"6","key":"177_CR13","doi-asserted-by":"publisher","first-page":"3299","DOI":"10.1073\/pnas.0434590100","volume":"100","author":"S Maretto","year":"2003","unstructured":"Maretto S, Cordenonsi M, Dupont S, Braghetta P, Broccoli V, Hassan AB, Volpin D, Bressan GM, Piccolo S: Mapping Wnt\/beta-catenin signaling during mouse development and in colorectal tumors. Proc Natl Acad Sci U S A. 2003, 100 (6): 3299-3304. 10.1073\/pnas.0434590100.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"16","key":"177_CR14","doi-asserted-by":"publisher","first-page":"8455","DOI":"10.1073\/pnas.93.16.8455","volume":"93","author":"PS Klein","year":"1996","unstructured":"Klein PS, Melton DA: A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci U S A. 1996, 93 (16): 8455-8459. 10.1073\/pnas.93.16.8455.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"177_CR15","doi-asserted-by":"crossref","first-page":"548","DOI":"10.2144\/02323st07","volume":"32","author":"L Wilson","year":"2002","unstructured":"Wilson L, Fathke C, Isik F: Tissue dispersion and flow cytometry for the cellular analysis of wound healing. Biotechniques. 2002, 32 (3): 548-551.","journal-title":"Biotechniques"},{"issue":"5306","key":"177_CR16","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.1126\/science.275.5306.1652","volume":"275","author":"X He","year":"1997","unstructured":"He X, Saint-Jeannet JP, Wang Y, Nathans J, Dawid I, Varmus H: A member of the Frizzled protein family mediating axis induction by Wnt- 5A. Science. 1997, 275 (5306): 1652-1654. 10.1126\/science.275.5306.1652.","journal-title":"Science"},{"issue":"5","key":"177_CR17","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/S0092-8674(04)00208-9","volume":"116","author":"AJ Wagers","year":"2004","unstructured":"Wagers AJ, Weissman IL: Plasticity of adult stem cells. Cell. 2004, 116 (5): 639-648. 10.1016\/S0092-8674(04)00208-9.","journal-title":"Cell"},{"issue":"6","key":"177_CR18","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1056\/NEJMra022361","volume":"349","author":"M Korbling","year":"2003","unstructured":"Korbling M, Estrov Z: Adult stem cells for tissue repair - a new therapeutic concept?. N Engl J Med. 2003, 349 (6): 570-582. 10.1056\/NEJMra022361.","journal-title":"N Engl J Med"},{"issue":"10","key":"177_CR19","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1101\/gad.1086903","volume":"17","author":"L Alonso","year":"2003","unstructured":"Alonso L, Fuchs E: Stem cells in the skin: waste not, Wnt not. Genes Dev. 2003, 17 (10): 1189-1200. 10.1101\/gad.1086903.","journal-title":"Genes Dev"},{"issue":"6893","key":"177_CR20","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/nature00870","volume":"418","author":"Y Jiang","year":"2002","unstructured":"Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM: Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002, 418 (6893): 41-49. 10.1038\/nature00870.","journal-title":"Nature"},{"issue":"9","key":"177_CR21","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1038\/ncb0901-778","volume":"3","author":"JG Toma","year":"2001","unstructured":"Toma JG, Akhavan M, Fernandes KJ, Barnabe-Heider F, Sadikot A, Kaplan DR, Miller FD: Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat Cell Biol. 2001, 3 (9): 778-784. 10.1038\/ncb0901-778.","journal-title":"Nat Cell Biol"},{"issue":"5457","key":"177_CR22","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1126\/science.287.5457.1427","volume":"287","author":"FM Watt","year":"2000","unstructured":"Watt FM, Hogan BL: Out of Eden: stem cells and their niches. Science. 2000, 287 (5457): 1427-1430. 10.1126\/science.287.5457.1427.","journal-title":"Science"},{"issue":"5457","key":"177_CR23","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1126\/science.287.5457.1433","volume":"287","author":"FH Gage","year":"2000","unstructured":"Gage FH: Mammalian neural stem cells. Science. 2000, 287 (5457): 1433-1438. 10.1126\/science.287.5457.1433.","journal-title":"Science"},{"issue":"13","key":"177_CR24","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1016\/S0960-9822(03)00396-8","volume":"13","author":"P Martin","year":"2003","unstructured":"Martin P, D'Souza D, Martin J, Grose R, Cooper L, Maki R, McKercher SR: Wound healing in the PU.1 null mouse--tissue repair is not dependent on inflammatory cells. Curr Biol. 2003, 13 (13): 1122-1128. 10.1016\/S0960-9822(03)00396-8.","journal-title":"Curr Biol"},{"issue":"19","key":"177_CR25","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1016\/S0960-9822(98)70443-9","volume":"8","author":"B St-Jacques","year":"1998","unstructured":"St-Jacques B, Dassule HR, Karavanova I, Botchkarev VA, Li J, Danielian PS, McMahon JA, Lewis PM, Paus R, McMahon AP: Sonic hedgehog signaling is essential for hair development. Curr Biol. 1998, 8 (19): 1058-1068. 10.1016\/S0960-9822(98)70443-9.","journal-title":"Curr Biol"},{"issue":"2","key":"177_CR26","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1101\/gad.1038103","volume":"17","author":"P Mill","year":"2003","unstructured":"Mill P, Mo R, Fu H, Grachtchouk M, Kim PC, Dlugosz AA, Hui CC: Sonic hedgehog-dependent activation of Gli2 is essential for embryonic hair follicle development. Genes Dev. 2003, 17 (2): 282-294. 10.1101\/gad.1038103.","journal-title":"Genes Dev"},{"issue":"2","key":"177_CR27","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/88889","volume":"28","author":"RL Waikel","year":"2001","unstructured":"Waikel RL, Kawachi Y, Waikel PA, Wang XJ, Roop DR: Deregulated expression of c-Myc depletes epidermal stem cells. Nat Genet. 2001, 28 (2): 165-168. 10.1038\/88889.","journal-title":"Nat Genet"},{"issue":"5","key":"177_CR28","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1111\/j.1346-8138.2004.tb00687.x","volume":"31","author":"KA Honeycutt","year":"2004","unstructured":"Honeycutt KA, Roop DR: c-Myc and epidermal stem cell fate determination. J Dermatol. 2004, 31 (5): 368-375.","journal-title":"J Dermatol"},{"issue":"1","key":"177_CR29","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1242\/dev.129.1.95","volume":"129","author":"C Niemann","year":"2002","unstructured":"Niemann C, Owens DM, Hulsken J, Birchmeier W, Watt FM: Expression of DeltaNLef1 in mouse epidermis results in differentiation of hair follicles into squamous epidermal cysts and formation of skin tumours. Development. 2002, 129 (1): 95-109.","journal-title":"Development"},{"issue":"8","key":"177_CR30","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1242\/dev.01052","volume":"131","author":"C Lo Celso","year":"2004","unstructured":"Lo Celso C, Prowse DM, Watt FM: Transient activation of beta-catenin signalling in adult mouse epidermis is sufficient to induce new hair follicles but continuous activation is required to maintain hair follicle tumours. Development. 2004, 131 (8): 1787-1799. 10.1242\/dev.01052.","journal-title":"Development"},{"issue":"3","key":"177_CR31","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/S1535-6108(02)00045-4","volume":"1","author":"AT Weeraratna","year":"2002","unstructured":"Weeraratna AT, Jiang Y, Hostetter G, Rosenblatt K, Duray P, Bittner M, Trent JM: Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma. Cancer Cell. 2002, 1 (3): 279-288. 10.1016\/S1535-6108(02)00045-4.","journal-title":"Cancer Cell"},{"issue":"4","key":"177_CR32","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1046\/j.1524-475X.2002.10405.x","volume":"10","author":"R Tsou","year":"2002","unstructured":"Tsou R, Fathke C, Wilson L, Wallace K, Gibran N, Isik F: Retroviral delivery of dominant-negative vascular endothelial growth factor receptor type 2 to murine wounds inhibits wound angiogenesis. Wound Repair Regen. 2002, 10 (4): 222-229. 10.1046\/j.1524-475X.2002.10405.x.","journal-title":"Wound Repair Regen"},{"issue":"2","key":"177_CR33","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1097\/00024382-200302000-00007","volume":"19","author":"NS Gibran","year":"2003","unstructured":"Gibran NS, Tamura R, Tsou R, Isik FF: Human dermal microvascular endothelial cells produce nerve growth factor: implications for wound repair. Shock. 2003, 19 (2): 127-130. 10.1097\/00024382-200302000-00007.","journal-title":"Shock"},{"issue":"1","key":"177_CR34","first-page":"14","volume":"58","author":"F Grignani","year":"1998","unstructured":"Grignani F, Kinsella T, Mencarelli A, Valtieri M, Riganelli D, Lanfrancone L, Peschle C, Nolan GP, Pelicci PG: High-efficiency gene transfer and selection of human hematopoietic progenitor cells with a hybrid EBV\/retroviral vector expressing the green fluorescence protein. Cancer Res. 1998, 58 (1): 14-19.","journal-title":"Cancer Res"},{"key":"177_CR35","unstructured":"Nolan G: . 2005, [http:\/\/www.stanford.edu\/group\/nolan\/]"}],"container-title":["BMC Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2121-7-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T17:47:50Z","timestamp":1630432070000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmolcellbiol.biomedcentral.com\/articles\/10.1186\/1471-2121-7-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,1,20]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,12]]}},"alternative-id":["177"],"URL":"https:\/\/doi.org\/10.1186\/1471-2121-7-4","relation":{},"ISSN":["1471-2121"],"issn-type":[{"value":"1471-2121","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,1,20]]},"assertion":[{"value":"19 April 2005","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2006","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2006","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"4"}}