信号动态控制果蝇早期胚胎中的细胞命运。
Signaling Dynamics Control Cell Fate in the Early Drosophila Embryo.
机构信息
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
出版信息
Dev Cell. 2019 Feb 11;48(3):361-370.e3. doi: 10.1016/j.devcel.2019.01.009.
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 endoderm-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.
Erk 丝裂原活化蛋白激酶在动物发育中发挥多种作用。其广泛的重复使用提出了一个难题：当单一激酶如 Erk 被激活时，发育中的细胞如何知道要采用哪种命运？我们将光遗传学控制与遗传扰动相结合，以剖析早期果蝇胚胎中 Erk 依赖性命运。我们发现 Erk 活性足以“向后转化”88%的胚胎，在该区域的所有细胞中诱导肠内胚层样基因表达和形态发生运动。肠内胚层命运的采用至少需要 1 小时的信号传递，而 30 分钟的 Erk 脉冲则指定了一种不同的外胚层细胞类型，中间神经母细胞。我们发现，内胚层-外胚层细胞命运的转变是由 Erk 活性的累积负荷控制的，而不是由单个脉冲的持续时间控制的。因此，果蝇胚胎具有一个经典的动态控制范例，其中 Erk 信号的时间曲线在不同的生理结果之间进行选择。
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