During early mammalian development, the first lineage decision separates the trophectoderm from the inner cell mass (ICM). How this first cell fate choice is made has been the subject of intense research, but remains incompletely understood. The transcription factor YAP has been identified as a key fate determinant: nuclear localisation of YAP drives expression of trophectoderm genes, while in the ICM, YAP is sequestered in the cytoplasm. Christophe Royer, Shankar Srinivas and colleagues set out to investigate whether cell shape and/or position within the early mouse embryo can regulate YAP localisation. They measure multiple parameters of cell geometry and assess correlations with YAP nuclear to cytoplasmic ratio (N/C YAP). They find that the proportion of exposed surface area of a blastomere correlates most strongly with N/C YAP. By manipulating cell geometry through embryo confinement experiments, they further demonstrate that cells can be induced to adopt one or other fate by modulating this parameter. Moreover they find that the correlation between exposed surface area and N/C YAP can be observed as early as the eight-cell stage – before other signs of fate determination. The authors propose that blastomeres are able to sense their proportion of exposed surface area, and that – through YAP localisation – this helps define the first cell fate choice.
