Figure 1. MCPyV sT expression in ectopic Merkel cells initiates MCC-like tumor development in mice.

A) Histology of epidermis from control and pre-term transgenic mouse embryos expressing MCPyV sT, Atoh1 or sT+Atoh1 driven by the Keratin 5 promoter compared to human intraepidermal MCC (MCC_IE). Control epidermis contains a single layer of basal cells (ba) with several layers of differentiating spinous (sp), granular (gr) and cornified (co) cells. Expression of sT alone leads to epidermal hyperplasia and dysplasia, Atoh1 alone drives ectopic Merkel cells (mc) within a hypoplastic epidermis, whereas co-expression of sT and Atoh1 leads to MCC-like tumors. B) Immunohistochemical staining for Merkel cell and MCC markers Sox2, K8 and K20. Appearances of tumor-like aggregates of cells and of K8 in paranuclear dots is restricted to mice expressing sT+Atoh1. C) Ki67 immunostaining shows high proliferative activity in multiple layers of epidermis only in sT-expressing mice. D) Co-immunofluorescence for phospho-Histone H3 (pHH3) and K8 indicates mitotic activity of K8-positive cells largely restricted to MCC-like tumor cells in sT+Atoh1 mice. Scale bars = 25 μm; scale bars for K8 (hi mag) = 10 μm.