Coppey Mathieu, Boettiger Alistair N, Berezhkovskii Alexander M, Shvartsman Stanislav Y
Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08540, USA.
Curr Biol. 2008 Jun 24;18(12):915-9. doi: 10.1016/j.cub.2008.05.034.
Patterning of the terminal regions of the Drosophila embryo relies on the gradient of phosphorylated ERK/MAPK (dpERK), which is controlled by the localized activation of the Torso receptor tyrosine kinase [1-4]. This model is supported by a large amount of data, but the gradient itself has never been quantified. We present the first measurements of the dpERK gradient and establish a new intracellular layer of its regulation. Based on the quantitative analysis of the spatial pattern of dpERK in mutants with different levels of Torso as well as the dynamics of the wild-type dpERK pattern, we propose that the terminal-patterning gradient is controlled by a cascade of diffusion-trapping modules. A ligand-trapping mechanism establishes a sharply localized pattern of the Torso receptor occupancy on the surface of the embryo. Inside the syncytial embryo, nuclei play the role of traps that localize diffusible dpERK. We argue that the length scale of the terminal-patterning gradient is determined mainly by the intracellular module.
果蝇胚胎末端区域的模式形成依赖于磷酸化的细胞外信号调节激酶/丝裂原活化蛋白激酶(dpERK)梯度,该梯度由躯干受体酪氨酸激酶的局部激活所控制[1-4]。大量数据支持这一模型,但该梯度本身从未被量化过。我们首次对dpERK梯度进行了测量,并建立了其调控的一个新的细胞内层次。基于对不同躯干水平突变体中dpERK空间模式的定量分析以及野生型dpERK模式的动态变化,我们提出末端模式形成梯度由一系列扩散捕获模块所控制。一种配体捕获机制在胚胎表面建立了躯干受体占据的高度局部化模式。在合胞体胚胎内部,细胞核起到捕获可扩散dpERK的作用。我们认为末端模式形成梯度的长度尺度主要由细胞内模块决定。