The skin epidermis is transformed during development, through stratification and differentiation, from a simple single-layered epithelium into a complex barrier just before birth. However, how epidermal stratification and the switch in cell fate from the basal to suprabasal keratinocytes are achieved at the molecular level remain elusive. Understanding the crucial cell fate switch is important for designing therapies for hyperproliferative human skin diseases such as psoriasis or atopic dermatitis, which may recapitulate developmental programs. Using dynamic growth and tissue measurements in the mouse, we recently proposed a two-phase model of epidermal stratification and development. In the first phase, the epidermal progenitors undergo a burst in proliferation around embryonic day E13.5 that leads to crowding in the basal layer and the onset of stratification, where cells are pushed upwards to form new suprabasal layers. In this study, our data show that active nuclear YAP staining of basal keratinocytes temporally correlates with their proliferation dynamics, particularly in the first phase. Moreover, the Notch downstream target HES1 was highly enriched in ~2% of the basal progenitors at the beginning of the second phase, suggesting that these cells potentially delaminate and migrate suprabasally to continuously supporting epidermal development. In addition, we generated a Krt10-mNeonGreen knockin suprabasal-reporter mouse line and used time-lapse imaging of the developing skin, which identified single cells delaminating and acquiring a suprabasal fate. Based on our data, we propose a working model whereby YAP/TAZ signaling drives proliferation to govern the first phase of epidermal stratification, whereas Notch signaling regulates the second phase through cellular delamination.

ESDR175 - Yap and Notch signaling activities correlate with the two phases of skin epidermal stratification during development

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.