Sequential oncogenic mutations influence cell competition.

At the initial stage of carcinogenesis, newly emerging transformed cells are often eliminated from epithelial layers via cell competition with the surrounding normal cells. For instance, when surrounded by normal cells, oncoprotein RasV12-transformed cells are extruded into the apical lumen of epithelia. During cancer development, multiple oncogenic mutations accumulate within epithelial tissues.

LGR4 is required for sequential molar development.

Tooth development requires proliferation, differentiation, and specific migration of dental epithelial cells, through well-organized signaling interactions with mesenchymal cells. Recently, it has been reported that leucine-rich repeat-containing G protein coupled receptor 4 (LGR4), the receptor of R-spondins, is expressed in many epithelial cells in various organs and tissues and is essential for organ development and stem cell maintenance. Here, we report that LGR4 contributes to the sequential development of molars in mice.