Romanos Michèle, Allio Guillaume, Roussigné Myriam, Combres Léa, Escalas Nathalie, Soula Cathy, Médevielle François, Steventon Benjamin, Trescases Ariane, Bénazéraf Bertrand
Molecular, Cellular and Developmental biology department (MCD), Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse, France.
Institut de Mathématiques de Toulouse UMR 5219, Université de Toulouse, Toulouse, France.
Elife. 2021 Oct 5;10:e66588. doi: 10.7554/eLife.66588.
Although cell-to-cell heterogeneity in gene and protein expression within cell populations has been widely documented, we know little about its biological functions. By studying progenitors of the posterior region of bird embryos, we found that expression levels of transcription factors Sox2 and Bra, respectively involved in neural tube (NT) and mesoderm specification, display a high degree of cell-to-cell heterogeneity. By combining forced expression and downregulation approaches with time-lapse imaging, we demonstrate that Sox2-to-Bra ratio guides progenitor's motility and their ability to stay in or exit the progenitor zone to integrate neural or mesodermal tissues. Indeed, high Bra levels confer high motility that pushes cells to join the paraxial mesoderm, while high levels of Sox2 tend to inhibit cell movement forcing cells to integrate the NT. Mathematical modeling captures the importance of cell motility regulation in this process and further suggests that randomness in Sox2/Bra cell-to-cell distribution favors cell rearrangements and tissue shape conservation.
尽管细胞群体内基因和蛋白质表达的细胞间异质性已被广泛记录，但我们对其生物学功能知之甚少。通过研究鸟类胚胎后部区域的祖细胞，我们发现分别参与神经管（NT）和中胚层特化的转录因子Sox2和Bra的表达水平表现出高度的细胞间异质性。通过将强制表达和下调方法与延时成像相结合，我们证明Sox2与Bra的比例指导祖细胞的运动能力以及它们留在祖细胞区或离开祖细胞区以整合神经或中胚层组织的能力。事实上，高水平的Bra赋予高运动性，促使细胞加入近轴中胚层，而高水平的Sox2倾向于抑制细胞运动，迫使细胞整合到神经管中。数学模型揭示了细胞运动调节在这一过程中的重要性，并进一步表明Sox2/Bra细胞间分布的随机性有利于细胞重排和组织形状的维持。
