In order to investigate the role of β-catenin in cell fate selection in specific regions of adult epidermis, I used three different promoters to over express N-terminally truncated, stabilised β-catenin fused to the ligand-binding domain of a mutant oestrogen receptor (ΔNβ-cateninER) in the epidermis of transgenic mice. The human keratin 1 (HK1) promoter targets cells in the interfollicular epidermis that are committed to terminal differentiation; the keratin 15 (K15) promoter targets stem cells in the hair bulge; and the truncated keratin 5 (ΔK5) promoter targets the basal layer cells of the hair bulb and sebaceous glands. Using topical applications of 4-hydroxytamoxifen (4OHT) β-catenin was activated at specific stages of the hair cycle and for different lengths of time. Resting hair follicles at K15ΔNβ-cateninER and ΔK5ΔNβ-cateninER mice were recruited into the growth phase of the hair cycle. In addition, ectopic hair follicles formed from the sebaceous glands of ΔK5ΔNβ-cateninER mice. The ectopic hair follicles often formed cyst-like structures, containing highly proliferative cells and cells that expressed hair keratins or sebocyte markers. Whilst a transient activation of β-catenin signalling is sufficient to trigger hair follicle morphogenesis, continuous β-catenin signalling is required to maintain the cyst like structures. No ectopic hair growth was seen in the K15ΔNβ-cateninER mice, although the bulge was seen to proliferate and show induction of β-catenin target genes. The HK1ΔNβ-cateninER mice never presented with a phenotype, which correlated with a failure of the transgene to induce downsteam factors such as Lef1. Wounding or treatment with vitamin A did not influence the response of the epidermis to β-catenin activation. However, vitamin D treatment reduced proliferation in both ΔK5ΔNβ-cateninER and K15ΔNβ-cateninER mice and stimulated differentiation of the ectopic hair follicles in ΔK5ΔNβ-cateninER mice.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:596275 |
| Date | January 2010 |
| Creators | Baker, C. M. |
| Publisher | University of Cambridge |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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