Signaling Dynamics Control Cell Fate in the Early Drosophila Embryo
Signaling Dynamics Control Cell Fate in the Early Drosophila Embryo
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DOI：
10.1016/j.devcel.2019.01.009
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发表时间：
2019-02-11
影响因子：
11.8
通讯作者：
Toettcher, Jared E.
中科院分区：
文献类型：
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作者：
Johnson, Heath E.;Toettcher, Jared E.
Erk 丝裂原激活蛋白激酶在动物发育中发挥着多种作用。它的广泛重复使用引发了一个难题：当像 Erk 这样的单一激酶被激活时，发育中的细胞如何知道采取哪种命运？我们将光遗传学控制与遗传扰动结合起来，剖析早期果蝇胚胎中依赖于 Erk 的命运。我们发现 Erk 活性足以“后置”88% 的胚胎，从而诱导该区域内所有细胞的肠道内胚层样基因表达和形态发生运动。肠道内胚层命运采用需要至少 1 小时的信号传导，而 30 分钟的 Erk 脉冲指定一种独特的外胚层细胞类型，即中间神经母细胞。我们发现内胚层-外胚层细胞命运转换是由 Erk 活性的累积负载控制的，而不是单个信号的持续时间。因此，果蝇胚胎具有动态控制的典型例子，其中 Erk 信号的时间分布在不同的生理结果之间进行选择。
The Erk mitogen-activated protein kinase plays diverse roles in animal development. Its widespread reuse raises a conundrum: when a single kinase like Erk is activated, how does a developing cell know which fate to adopt? We combine optogenetic control with genetic perturbations to dissect Erk-dependent fates in the early Drosophila embryo. We find that Erk activity is sufficient to "posteriorize'' 88% of the embryo, inducing gut endoderm-like gene expression and morphogenetic movements in all cells within this region. Gut endoderm fate adoption requires at least 1 h of signaling, whereas a 30-min Erk pulse specifies a distinct ectodermal cell type, intermediate neuroblasts. We find that the endo-derm-ectoderm cell fate switch is controlled by the cumulative load of Erk activity, not the duration of a single pulse. The fly embryo thus harbors a classic example of dynamic control, where the temporal profile of Erk signaling selects between distinct physiological outcomes.