Golembo M, Raz E, Shilo B Z
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Development. 1996 Nov;122(11):3363-70. doi: 10.1242/dev.122.11.3363.
The Drosophila EGF receptor (DER) is activated by secreted Spitz to induce different cell fates in the ventral ectoderm. Processing of the precursor transmembrane Spitz to generate the secreted form was shown to be the limiting event, but the cells in which processing takes place and the mechanism that may generate a gradient of secreted Spitz in the ectoderm were not known. The ectodermal defects in single minded (sim) mutant embryos, in which the midline fails to develop, suggested that the midline cells contribute to patterning of the ventral ectoderm. This work shows that the midline provides the site for Spitz expression and processing. The Rhomboid and Star proteins are also expressed and required in the midline. The ectodermal defects of spitz, rho or Star mutant embryos could be rescued by inducing the expression of the respective normal genes only in the midline cells. Rho and Star thus function non-autonomously, and may be required for the production or processing of the Spitz precursor. Secreted Spitz is the only sim-dependent contribution of the midline to patterning the ectoderm, since the ventral defects observed in sim mutant embryos can be overcome by expression of secreted Spitz in the ectoderm. While ectopic expression of secreted Spitz in the ectoderm or mesoderm gave rise to ventralization of the embryo, increased expression of secreted Spitz in the midline did not lead to alterations in ectoderm patterning. A mechanism for adjustment to variable levels of secreted Spitz emanating from the midline may be provided by Argos, which forms an inhibitory feedback loop for DER activation. The production of secreted Spitz in the midline, may provide a stable source for graded DER activation in the ventral ectoderm.
果蝇表皮生长因子受体（DER）通过分泌的斯皮茨蛋白（Spitz）被激活，从而诱导腹侧外胚层产生不同的细胞命运。研究表明，将跨膜前体斯皮茨蛋白加工成分泌形式是一个限制因素，但加工发生的细胞以及在外胚层中产生分泌型斯皮茨蛋白梯度的机制尚不清楚。在单 minded（sim）突变胚胎中，中线无法发育，其外胚层缺陷表明中线细胞有助于腹侧外胚层的模式形成。这项研究表明，中线为斯皮茨蛋白的表达和加工提供了场所。菱形蛋白（Rhomboid）和星状蛋白（Star）也在中线表达且是必需的。仅在中线细胞中诱导各自正常基因的表达，就可以挽救 spitz、rho 或 Star 突变胚胎的外胚层缺陷。因此，Rho 和 Star 发挥非自主功能，可能是斯皮茨蛋白前体产生或加工所必需的。分泌型斯皮茨蛋白是中线对模式化外胚层的唯一依赖于 sim 的贡献，因为在 sim 突变胚胎中观察到的腹侧缺陷可以通过在外胚层中表达分泌型斯皮茨蛋白来克服。虽然在外胚层或中胚层中异位表达分泌型斯皮茨蛋白会导致胚胎腹侧化，但在中线增加分泌型斯皮茨蛋白的表达并不会导致外胚层模式的改变。Argos 可能提供了一种机制，用于调节从中线发出的不同水平的分泌型斯皮茨蛋白，它形成了一个抑制 DER 激活的反馈回路。中线中分泌型斯皮茨蛋白的产生，可能为腹侧外胚层中分级 DER 激活提供一个稳定的来源。
