| First Author | Akladios B | Year | 2017 |
| Journal | J Invest Dermatol | Volume | 137 |
| Issue | 3 | Pages | 716-726 |
| PubMed ID | 27816394 | Mgi Jnum | J:240048 |
| Mgi Id | MGI:5882264 | Doi | 10.1016/j.jid.2016.10.029 |
| Citation | Akladios B, et al. (2017) Epidermal YAP2-5SA-DeltaC Drives beta-Catenin Activation to Promote Keratinocyte Proliferation in Mouse Skin In Vivo. J Invest Dermatol 137(3):716-726 |
| abstractText | 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 beta-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 beta-catenin and reduced keratinocyte numbers in vitro. In addition, we found that in the hyperplastic epidermis of YAP2-5SA-DeltaC mice, the mutant YAP2-5SA-DeltaC protein was predominantly localized in the keratinocyte nuclei and caused increased expression of activated nuclear beta-catenin. Accordingly, beta-catenin transcriptional activity was elevated in the skin of live YAP2-5SA-DeltaC/TOPFLASH mice. Lastly, loss of beta-catenin in basal keratinocytes of YAP2-5SA-DeltaC/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-DeltaC drives beta-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 beta-catenin activity. |
