John von Neumann Institute for Computing, Jülich Supercomputer Centre, Forschungszentrum Jülich, Jülich, Germany.
Living Systems Institute, School of Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom.
PLoS Comput Biol. 2020 Jun 24;16(6):e1007417. doi: 10.1371/journal.pcbi.1007417. eCollection 2020 Jun.
During embryogenesis, morphogens form a concentration gradient in responsive tissue, which is then translated into a spatial cellular pattern. The mechanisms by which morphogens spread through a tissue to establish such a morphogenetic field remain elusive. Here, we investigate by mutually complementary simulations and in vivo experiments how Wnt morphogen transport by cytonemes differs from typically assumed diffusion-based transport for patterning of highly dynamic tissue such as the neural plate in zebrafish. Stochasticity strongly influences fate acquisition at the single cell level and results in fluctuating boundaries between pattern regions. Stable patterning can be achieved by sorting through concentration dependent cell migration and apoptosis, independent of the morphogen transport mechanism. We show that Wnt transport by cytonemes achieves distinct Wnt thresholds for the brain primordia earlier compared with diffusion-based transport. We conclude that a cytoneme-mediated morphogen transport together with directed cell sorting is a potentially favored mechanism to establish morphogen gradients in rapidly expanding developmental systems.
在胚胎发生过程中，形态发生素在反应组织中形成浓度梯度，然后转化为空间细胞模式。形态发生素如何在组织中扩散以建立这种形态发生场的机制仍然难以捉摸。在这里，我们通过相互补充的模拟和体内实验研究了细胞丝状伪足如何不同于通常假设的扩散基运输，从而对斑马鱼中神经板等高度动态组织的模式形成进行运输。随机性在单细胞水平上强烈影响命运的获得，并导致模式区域之间的边界波动。通过浓度依赖性细胞迁移和细胞凋亡的分选，可以实现稳定的图案形成，而与形态发生素的运输机制无关。我们表明，与基于扩散的运输相比，细胞丝状伪足运输的 Wnt 更早地达到大脑原基的独特 Wnt 阈值。我们得出结论，与扩散基运输相比，细胞丝状伪足介导的形态发生素运输与定向细胞分选相结合是在快速扩张的发育系统中建立形态发生素梯度的一种潜在有利机制。
