Dll1 Marks Cells of Origin of Ras-Induced Cancer in Mouse Squamous Epithelia

The Notch signaling pathway has been implicated in homeostasis and disease, including cancer, in various tissues. Moreover, it has been involved both in stem cell maintenance and differentiation, in a context-dependent manner. Stem/progenitor cells, on the other hand, have long been suspected to be the cells of origin in various malignancies. In order to gain insight in the role of the Notch ligand Dll1 in mouse development, we generated a knock-in line expressing an inducible Cre recombinase. We have employed in vivo approaches in mice to genetically mark rare subpopulations of cells expressing Dll1 in various adult tissues. Moreover, we conditionally expressed a constitutively active Ras oncoprotein in these cells and showed that within days, mice develop squamous neoplasias in the skin, as well as in the stomach.