Golembo M, Schweitzer R, Freeman M, Shilo B Z
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Development. 1996 Jan;122(1):223-30. doi: 10.1242/dev.122.1.223.
Argos is a secreted molecule with an atypical EGF motif. It was recently shown to function as an inhibitor of the signaling triggered by the Drosophila EGF receptor (DER). In this work, we determine the contribution of Argos to the establishment of cell fates in the embryonic ventral ectoderm. Graded activation of DER is essential for patterning the ventral ectoderm. argos mutant embryos show expansion of ventral cell fates suggesting hyperactivation of the DER pathway. In the embryonic ventral ectoderm, argos is expressed in the ventralmost row of cells. We show that argos expression in the ventral ectoderm is induced by the DER pathway: argos is not expressed in DER mutant embryos, while it is ectopically expressed in the entire ventral ectoderm following ubiquitous activation of the DER pathway. argos expression appears to be triggered directly by the DER pathway, since induction can also be observed in cell culture, following activation of DER by its ligand, Spitz. Argos therefore functions in a sequential manner, to restrict the duration and level of DER signaling. This type of inhibitory feedback loop may represent a general paradigm for signaling pathways inducing diverse cell fates within a population of non-committed cells.
阿高斯是一种具有非典型表皮生长因子（EGF）基序的分泌分子。最近的研究表明，它作为果蝇表皮生长因子受体（DER）触发信号的抑制剂发挥作用。在这项研究中，我们确定了阿高斯在胚胎腹侧外胚层细胞命运确立过程中的作用。DER的分级激活对于腹侧外胚层的模式形成至关重要。阿高斯突变体胚胎显示腹侧细胞命运扩展，提示DER信号通路过度激活。在胚胎腹侧外胚层中，阿高斯在最腹侧的一排细胞中表达。我们发现腹侧外胚层中阿高斯的表达是由DER信号通路诱导的：在DER突变体胚胎中不表达阿高斯，而在DER信号通路普遍激活后，它在整个腹侧外胚层中异位表达。阿高斯的表达似乎是由DER信号通路直接触发的，因为在细胞培养中，当DER被其配体斯皮茨激活后也能观察到诱导现象。因此，阿高斯以一种顺序性的方式发挥作用，来限制DER信号传导的持续时间和水平。这种抑制性反馈回路可能代表了一种普遍模式，用于在一群未分化细胞中诱导不同细胞命运的信号通路。
