Cell-to-cell heterogeneity in Sox2 and Brachyury expression guides progenitor destiny by controlling their movements

Although cell-to-cell heterogeneity in gene and protein expression has been widely documented within a given cell population, little is known about its potential biological functions. We addressed this issue by studying posterior progenitors, an embryonic cell population that is central to vertebrate posterior axis formation. These progenitors are able to maintain themselves within the posterior region of the embryo or to exit this region to participate in the formation of neural tube or paraxial mesoderm tissues. Posterior progenitors are known to co-express transcription factors related to neural and mesodermal lineages, e.g. Sox2 and Brachyury (Bra), respectively. In this study, we find that expression levels of Sox2 and Bra proteins display a high degree of variability among posterior progenitors of the quail embryo, therefore highlighting spatial heterogeneity of this cell population. By over-expression/down-regulation experiments and time-lapse imaging, we show that Sox2 and Bra are both involved in controlling progenitor motility, acting however in an opposite way: while Bra is necessary to progenitor motion, Sox2 tends to inhibit cell movement. Combining mathematical modeling and experimental approaches, we provide evidence that the spatial heterogeneity of posterior progenitors, with regards to their expression levels of Sox2 and Bra and thus to their motile properties, is fundamental to maintain a pool of resident progenitors while others segregate to contribute to tissue formation. As a whole, our work reveals that heterogeneity among a population of progenitor cells is critical to ensure robust multi-tissue morphogenesis