Epidermal YAP2-5SA-ΔC drives β-catenin activation to promote keratinocyte proliferation in mouse skin in vivo

Akladios, Bassem, Mendoza-Reinoso, Veronica, Samuel, Michael S., Hardeman, Edna C., Khosrotehrani, Kiarash, Key, Brian and Beverdam, Annemiek (2017) Epidermal YAP2-5SA-ΔC drives β-catenin activation to promote keratinocyte proliferation in mouse skin in vivo. Journal of Investigative Dermatology, 137 3: 716-726. doi:10.1016/j.jid.2016.10.029


Author Akladios, Bassem
Mendoza-Reinoso, Veronica
Samuel, Michael S.
Hardeman, Edna C.
Khosrotehrani, Kiarash
Key, Brian
Beverdam, Annemiek
Title Epidermal YAP2-5SA-ΔC drives β-catenin activation to promote keratinocyte proliferation in mouse skin in vivo
Journal name Journal of Investigative Dermatology   Check publisher's open access policy
ISSN 1523-1747
0022-202X
Publication date 2017-03-01
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.jid.2016.10.029
Open Access Status Not yet assessed
Volume 137
Issue 3
Start page 716
End page 726
Total pages 11
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2018
Language eng
Formatted abstract
The epidermis is a highly regenerative tissue. YAP is a pivotal regulator of stem/progenitor cells in tissue regeneration, including in the epidermis. The molecular mechanisms downstream of YAP that activate epidermal cell proliferation remain largely unknown. We found that YAP and β-catenin co-localize in the nuclei of keratinocytes in the regenerating epidermis in vivo and in proliferating HaCaT keratinocytes in vitro. Inactivation of YAP in HaCaT keratinocytes resulted in reduced activated β-catenin and reduced keratinocyte numbers in vitro. In addition, we found that in the hyperplastic epidermis of YAP2-5SA-ΔC mice, the mutant YAP2-5SA-ΔC protein was predominantly localized in the keratinocyte nuclei and caused increased expression of activated nuclear β-catenin. Accordingly, β-catenin transcriptional activity was elevated in the skin of live YAP2-5SA-ΔC/TOPFLASH mice. Lastly, loss of β-catenin in basal keratinocytes of YAP2-5SA-ΔC/K14-creERT/CtnnB1–/– mice resulted in reduced proliferation of basal keratinocytes and a striking rescue of the hyperplastic abnormalities. Taken together, our work shows that YAP2-5SA-ΔC drives β-catenin activity to promote basal keratinocyte proliferation in the mouse skin in vivo. Our data shine new light on the etiology of regenerative dermatological disorders and other human diseases that display increased YAP and β-catenin activity.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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