Robust Wnt signaling is maintained by a Wg protein gradient and Fz2 receptor activity in the developing Drosophila wing
Robust Wnt signaling is maintained by a Wg protein gradient and Fz2 receptor activity in the developing Drosophila wing
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DOI：
10.1242/dev.174789
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发表时间：
2019-08-01
期刊：
影响因子：
4.6
通讯作者：
Boutros, Michael
中科院分区：
文献类型：
--
作者：
Chaudhary, Varun;Hingole, Swapnil;Boutros, Michael
Wnt是在所有后生动物发育过程中调节细胞命运的分泌蛋白。Wnt蛋白被提议分布在几个细胞中，以直接在一定距离处激活信号。在果蝇翅上皮细胞中，观察到Wnt 1同源物无翅（Wg）的细胞外梯度延伸到远离生产细胞的几个细胞。然而，令人惊讶的是，还显示了膜栓系的Neurotactin-Wg融合蛋白（NRT-Wg）可以在很大程度上取代内源性Wg，导致翅膀的正确图案化。因此，Wg的功能范围以及正确的组织图案化是否需要Wg扩散仍然存在争议。在这里，通过捕获远离来源的细胞上分泌的Wg，我们表明Wg在高达11个细胞直径的距离上起作用以诱导信号传导。此外，位于细胞外Wg到达范围之外的细胞依赖于Frizzled 2受体来维持信号传导。Frizzled 2表达在Wg分泌不存在的情况下增加，并且是维持NRT-wg翼盘中的信号传导和细胞存活所需的。总之，这些结果提供了对在增殖组织中实现稳健Wnt信号传导的机制的深入了解。
Wnts are secreted proteins that regulate cell fate during development of all metazoans. Wnt proteins were proposed to spread over several cells to activate signaling directly at a distance. In the Drosophila wing epithelium, an extracellular gradient of the Wnt1 homolog Wingless (Wg) was observed extending over several cells away from producing cells. Surprisingly, however, it was also shown that a membrane-tethered Neurotactin-Wg fusion protein (NRT-Wg) can largely replace endogenous Wg, leading to proper patterning of the wing. Therefore, the functional range of Wg and whether Wg spreading is required for correct tissue patterning remains controversial. Here, by capturing secreted Wg on cells away from the source, we show that Wg acts over a distance of up to 11 cell diameters to induce signaling. Furthermore, cells located outside the reach of extracellular Wg depend on the Frizzled2 receptor to maintain signaling. Frizzled2 expression is increased in the absence of Wg secretion and is required to maintain signaling and cell survival in NRT-wg wing discs. Together, these results provide insight into the mechanisms by which robust Wnt signaling is achieved in proliferating tissues.