Strigini M, Cohen S M
European Molecular Biology Laboratory, Heidelberg, 69117, Germany.
Curr Biol. 2000 Mar 23;10(6):293-300. doi: 10.1016/s0960-9822(00)00378-x.
Secreted signaling proteins of the Wingless (Wg)/Wnt, Hedgehog and bone morphogenetic protein (BMP)/Decapentaplegic (Dpp) families function as morphogens to control growth and pattern formation during development. Although these proteins have been shown to act directly on distant cells in the developing limbs of the fruit fly Drosophila, little is known about how ligand gradients form in vivo. Wg protein is found in vesicles in Wg-responsive cells in the embryo and imaginal discs. It has been proposed that Wg may be transported by a vesicle-mediated mechanism.
A novel method to visualize extracellular Wg protein was used to show that Wg forms an unstable gradient on the basolateral surface of the wing imaginal disc epithelium. Wg movement did not require internalization by dynamin-mediated endocytosis. Dynamin activity was, however, required for Wg secretion. By reversibly blocking Wg secretion, we found that Wg moves rapidly to form a long-range extracellular gradient.
The Wg morphogen gradient forms by rapid movement of ligand through the extracellular space, and depends on continuous secretion and rapid turnover. Endocytosis is not required for Wg movement, but contributes to shaping the gradient by removing extracellular Wg. We propose that the extracellular Wg gradient forms by diffusion.
无翅（Wg）/Wnt、刺猬索尼克（Hedgehog）和骨形态发生蛋白（BMP）/脱五体（Dpp）家族的分泌信号蛋白作为形态发生素，在发育过程中控制生长和模式形成。尽管这些蛋白已被证明可直接作用于果蝇发育肢体中的远距离细胞，但对于配体梯度在体内如何形成却知之甚少。Wg蛋白存在于胚胎和成虫盘的Wg反应性细胞的囊泡中。有人提出Wg可能通过囊泡介导的机制进行运输。
一种可视化细胞外Wg蛋白的新方法表明，Wg在翅成虫盘上皮的基底外侧表面形成不稳定梯度。Wg的移动不需要通过发动蛋白介导的内吞作用进行内化。然而，发动蛋白活性是Wg分泌所必需的。通过可逆地阻断Wg分泌，我们发现Wg迅速移动以形成长距离细胞外梯度。
Wg形态发生素梯度通过配体在细胞外空间的快速移动形成，并且依赖于持续分泌和快速周转。内吞作用不是Wg移动所必需的，但通过去除细胞外Wg有助于形成梯度。我们提出细胞外Wg梯度是通过扩散形成的。
