Institute of Science and Technology Austria, 3400 Klosterneuburg, Austria.
Institute of Science and Technology Austria, 3400 Klosterneuburg, Austria.
Dev Cell. 2017 Oct 23;43(2):198-211.e12. doi: 10.1016/j.devcel.2017.09.014. Epub 2017 Oct 12.
Cell-cell contact formation constitutes an essential step in evolution, leading to the differentiation of specialized cell types. However, remarkably little is known about whether and how the interplay between contact formation and fate specification affects development. Here, we identify a positive feedback loop between cell-cell contact duration, morphogen signaling, and mesendoderm cell-fate specification during zebrafish gastrulation. We show that long-lasting cell-cell contacts enhance the competence of prechordal plate (ppl) progenitor cells to respond to Nodal signaling, required for ppl cell-fate specification. We further show that Nodal signaling promotes ppl cell-cell contact duration, generating a positive feedback loop between ppl cell-cell contact duration and cell-fate specification. Finally, by combining mathematical modeling and experimentation, we show that this feedback determines whether anterior axial mesendoderm cells become ppl or, instead, turn into endoderm. Thus, the interdependent activities of cell-cell signaling and contact formation control fate diversification within the developing embryo.
细胞间接触的形成是进化过程中的一个基本步骤，导致了特化细胞类型的分化。然而，人们对接触形成和命运特化之间的相互作用是否以及如何影响发育知之甚少。在这里，我们在斑马鱼原肠胚形成过程中发现了细胞间接触持续时间、形态发生素信号和中胚层细胞命运特化之间的正反馈回路。我们表明，持久的细胞间接触增强了前翼板（ppl）祖细胞对 Nodal 信号的反应能力，这是 ppl 细胞命运特化所必需的。我们进一步表明，Nodal 信号促进 ppl 细胞间接触持续时间，在 ppl 细胞间接触持续时间和细胞命运特化之间产生正反馈回路。最后，通过结合数学建模和实验，我们表明这种反馈决定了前轴向中胚层细胞是成为 ppl，还是转变成内胚层。因此，细胞间信号和接触形成的相互依存活动控制了胚胎发育过程中命运的多样化。
