Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
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。