1. Developmental Biology
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Cell Fate Choice: Survival of the fattest

  1. Sophie M Morgani  Is a corresponding author
  2. Joshua M Brickman  Is a corresponding author
  1. University of Copenhagen, Denmark
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Cite this article as: eLife 2013;2:e01760 doi: 10.7554/eLife.01760
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Potential mechanisms for introducing bias into lineage priming.

When the amoeba D. discoideum is deprived of nutrients, it responds by forming a multicellular fruiting body made up of stalk and spore cells. The decision to become a stalk cell is induced by the signalling molecule DIF, and the nutrient history of each cell influences the likelihood that it will respond to DIF and adopt a particular fate. A similar situation arises in the early mouse embryo where cells can choose between becoming epiblast or primitive endoderm (PrE) cells, with the growth factor FGF promoting a PrE fate. The process can be visualized as a seesaw, with the nutrient history influencing the position of the fulcrum and, therefore, the likelihood that a cell will tipped towards a particular fate when exposed to DIF or FGF. In this way, the nutrient history of individual cells can establish precursor populations that are likely to become a stalk cell or a spore cell. Chattwood, Nagayama and co-workers now show that nutrient history affects the level of a protein called RasD in Dictyostelium, which in turn influences the ability of a cell to respond to DIF: high levels of RasD correspond to the fulcrum being closer to the left end of the seesaw (shaded triangle), so that the cells are primed to become stalk cells and exposure to DIF (solid red arrow) is more likely to lead to them becoming stalk cells. However, the primed state of these cells is not fixed because RasD expression can change based on nutrient history and the fulcrum can return to the right (dashed triangle), where cells are primed to become spore cells. When the fulcrum is positioned on the right, the cells are primed, but their fate is not determined because they can still become stalk cells if treated with high levels of DIF (dashed red arrow). In mice, a receptor called FGFR2 and a signalling molecule called FGF influence cell fate in a similar way to RasD and DIF in Dictyostelium. This suggests the intriguing possibility that nutrient history could influence the choice between epiblast and PrE lineages.

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