Cell competition and the regulation of robustness of growth during early mouse development

During the early stages of mammalian embryonic differentiation a vast array of cellular changes take place, including a dramatic increase in the proliferation rate and a rewiring of the transcriptional, epigenetic, metabolic and signalling networks. The dimension of these changes and the requirement for their timing to be carefully orchestrated implies that stringent quality control mechanisms must be in place to ensure the elimination of aberrant cells prior to the specification of the germline. Here I will discuss the work my laboratory has done to unravel the mechanism of elimination of non-lethally damaged cells during differentiation. I will present evidence to show that during embryonic differentiation, cells with mild forms of cellular damage, such as mis-patterning or karyotypical abnormalities are recognised as a less-fit by their neighbours that induce the elimination of these damaged cells. I will discuss how during this process the interplay of signalling and metabolic pathways governs the competitive interactions that ensue between cells with different fitness levels, as well as the implications of these interactions for the growth and patterning of the developing embryo.