Cell-to-cell heterogeneity in Sox2 and Brachyury expression ratios guides progenitor destiny by controlling their motility
| Autor: | Ben Steventon, Ariane Trescases, Nathalie Escalas, Cathy Soula, Léa Combres, Francois Médevielle, Michèle Romanos, Guillaume Allio, Bertrand Bénazéraf |
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| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
Brachyury Mesoderm education.field_of_study Population Neural tube Biology Cell biology 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure SOX2 embryonic structures medicine Paraxial mesoderm Progenitor cell education 030217 neurology & neurosurgery 030304 developmental biology Progenitor |
| DOI: | 10.1101/2020.11.18.388611 |
| Popis: | Although cell-to-cell heterogeneity in gene and protein expression within cell populations has been widely documented, we know little about its potential biological functions. We addressed this issue by studying progenitors that populate the posterior region of the vertebrate embryos, a cell population known for its capacity to self-renew or to contribute to the formation of the neural tube and paraxial mesoderm tissues. Posterior progenitors are characterized by the co-expression of Sox2 and Brachyury (Bra), two transcription factors related to neural and mesodermal lineages, respectively. In this study, we show that the respective levels of Sox2 and Bra proteins display a high degree of variability among posterior progenitors of the quail embryo. By developing forced expression and downregulation approaches, we further provide evidence that the value of the Sox2-to-Bra ratio in a given progenitor directs its choice of staying in place or exit the progenitor zone to generate neural or mesodermal cells. Time-lapse imaging together with mathematical modeling then reveal that variations of the Sox2-to-Bra ratio confer these cells heterogeneous motile behaviors. While high Bra levels display high motile properties that push cells to join the mesoderm, high levels of Sox2 tend to inhibit cell movement making cells get integrated into the neural tube. Our work thus provides evidence that the spatial heterogeneity of posterior progenitors, with regards to their relative contents 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. More broadly, our work reveals that heterogeneity among a population of progenitor cells is critical to ensure robust multi-tissue morphogenesis. |
| Databáze: | OpenAIRE |
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