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First published online March 30, 2004
doi: 10.1242/10.1242/dev.01052
Keratinocyte Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK
Author for correspondence (e-mail:
fiona.watt{at}cancer.org.uk)
Accepted 22 December 2003
When ß-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
ß-catenin-induced lineage conversion without prior embryonic priming. We
fused N-terminally truncated, stabilised ß-catenin to the ligand-binding
domain of a mutant oestrogen receptor (
Nß-cateninER).
Nß-cateninER was expressed in the epidermis of transgenic mice
under the control of the keratin 14 promoter and ß-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 ß-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
ß-catenin signalling is required to maintain hair follicle tumours.
Key words: Stem cells, Differentiation, Trichofolliculoma, ß-catenin
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