Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Cell Rep. 2018 Jul 3;24(1):66-78.e8. doi: 10.1016/j.celrep.2018.06.023.
Signal gradients encode instructive information for numerous decision-making processes during embryonic development. A striking example of precise, scalable tissue-level patterning is the segmentation of somites-the precursors of the vertebral column-during which the fibroblast growth factor (FGF), Wnt, and retinoic acid (RA) pathways establish spatial gradients. Despite decades of studies proposing roles for all three pathways, the dynamic feature of these gradients that encodes instructive information determining segment sizes remained elusive. We developed a non-elongating tail explant system, integrated quantitative measurements with computational modeling, and tested alternative models to show that positional information is encoded solely by spatial fold change (SFC) in FGF signal output. Neighboring cells measure SFC to accurately position the determination front and thus determine segment size. The SFC model successfully recapitulates results of spatiotemporal perturbation experiments on both explants and intact embryos, and it shows that Wnt signaling acts permissively upstream of FGF signaling and that RA gradient is dispensable.
信号梯度为胚胎发育过程中的许多决策过程提供了有指导意义的信息。一个精确的、可扩展的组织水平模式的显著例子是体节的分割——脊椎的前体，在此期间，成纤维细胞生长因子（FGF）、Wnt 和视黄酸（RA）途径建立了空间梯度。尽管数十年来的研究提出了这三种途径的作用，但决定体节大小的有指导意义的信息的这些梯度的动态特征仍然难以捉摸。我们开发了一个非伸长的尾巴外植体系统，将定量测量与计算模型相结合，并测试了替代模型，以表明位置信息仅由 FGF 信号输出的空间折叠变化（SFC）编码。相邻细胞测量 SFC 以准确定位决定前沿，从而确定体节大小。SFC 模型成功地再现了外植体和完整胚胎时空扰动实验的结果，它表明 Wnt 信号在前馈 FGF 信号的上游起许可作用，而 RA 梯度是可有可无的。
