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
- PMID: 15084463
- DOI: 10.1242/dev.01052
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
Abstract
When beta-catenin signalling is disturbed from mid-gestation onwards lineage commitment is profoundly altered in postnatal mouse epidermis. We have investigated whether adult epidermis has the capacity for beta-catenin-induced lineage conversion without prior embryonic priming. We fused N-terminally truncated, stabilised beta-catenin to the ligand-binding domain of a mutant oestrogen receptor (DeltaNbeta-cateninER). DeltaNbeta-cateninER was expressed in the epidermis of transgenic mice under the control of the keratin 14 promoter and beta-catenin activity was induced in adult epidermis by topical application of 4-hydroxytamoxifen (4OHT). Within 7 days of daily 4OHT treatment resting hair follicles were recruited into the hair growth cycle and epithelial outgrowths formed from existing hair follicles and from interfollicular epidermis. The outgrowths expressed Sonic hedgehog, Patched and markers of hair follicle differentiation, indicative of de novo follicle formation. The interfollicular epidermal differentiation program was largely unaffected but after an initial wave of sebaceous gland duplication sebocyte differentiation was inhibited. A single application of 4OHT was as effective as repeated doses in inducing new follicles and growth of existing follicles. Treatment of epidermis with 4OHT for 21 days resulted in conversion of hair follicles to benign tumours resembling trichofolliculomas. The tumours were dependent on continuous activation of beta-catenin and by 28 days after removal of the drug they had largely regressed. We conclude that interfollicular epidermis and sebaceous glands retain the ability to be reprogrammed in adult life and that continuous beta-catenin signalling is required to maintain hair follicle tumours.
Similar articles
-
Beta-catenin and Hedgehog signal strength can specify number and location of hair follicles in adult epidermis without recruitment of bulge stem cells.Dev Cell. 2005 Jul;9(1):121-31. doi: 10.1016/j.devcel.2005.04.013. Dev Cell. 2005. PMID: 15992546
-
Dynamic regulation of retinoic acid-binding proteins in developing, adult and neoplastic skin reveals roles for beta-catenin and Notch signalling.Dev Biol. 2008 Dec 1;324(1):55-67. doi: 10.1016/j.ydbio.2008.08.034. Epub 2008 Sep 12. Dev Biol. 2008. PMID: 18805411
-
Differential sensitivity of epidermal cell subpopulations to beta-catenin-induced ectopic hair follicle formation.Dev Biol. 2010 Jul 1;343(1-2):40-50. doi: 10.1016/j.ydbio.2010.04.005. Epub 2010 Apr 14. Dev Biol. 2010. PMID: 20398648 Free PMC article.
-
Beauty is skin deep: the fascinating biology of the epidermis and its appendages.Harvey Lect. 1998-1999;94:47-77. Harvey Lect. 1998. PMID: 11070952 Review.
-
Monstrous attempts at adnexogenesis: regulating hair follicle progenitors through Sonic hedgehog signaling.Curr Opin Genet Dev. 2001 Oct;11(5):541-6. doi: 10.1016/s0959-437x(00)00230-6. Curr Opin Genet Dev. 2001. PMID: 11532396 Review.
Cited by
-
Beta-catenin (CTNNB1) induces Bmp expression in urogenital sinus epithelium and participates in prostatic bud initiation and patterning.Dev Biol. 2013 Apr 15;376(2):125-35. doi: 10.1016/j.ydbio.2013.01.034. Epub 2013 Feb 8. Dev Biol. 2013. PMID: 23396188 Free PMC article.
-
Deciphering principles of morphogenesis from temporal and spatial patterns on the integument.Dev Dyn. 2015 Aug;244(8):905-20. doi: 10.1002/dvdy.24281. Epub 2015 Jul 6. Dev Dyn. 2015. PMID: 25858668 Free PMC article.
-
Polyclonal origin and hair induction ability of dermal papillae in neonatal and adult mouse back skin.Dev Biol. 2012 Jun 15;366(2):290-7. doi: 10.1016/j.ydbio.2012.03.016. Epub 2012 Apr 14. Dev Biol. 2012. PMID: 22537489 Free PMC article.
-
Hair follicle: a novel source of multipotent stem cells for tissue engineering and regenerative medicine.Tissue Eng Part B Rev. 2013 Aug;19(4):265-78. doi: 10.1089/ten.TEB.2012.0422. Epub 2013 Jan 3. Tissue Eng Part B Rev. 2013. PMID: 23157470 Free PMC article.
-
Wnt signaling induces epithelial differentiation during cutaneous wound healing.BMC Cell Biol. 2006 Jan 20;7:4. doi: 10.1186/1471-2121-7-4. BMC Cell Biol. 2006. PMID: 16426441 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
