Hacohen N, Kramer S, Sutherland D, Hiromi Y, Krasnow M A
Howard Hughes Medical Institute, Department of Biochemistry, Stanford University School of Medicine, California 94305-5307, USA.
Cell. 1998 Jan 23;92(2):253-63. doi: 10.1016/s0092-8674(00)80919-8.
Antagonists of several growth factor signaling pathways play important roles in developmental patterning by limiting the range of the cognate inducer. Here, we describe an antagonist of FGF signaling that patterns apical branching of the Drosophila airways. In wild-type embryos, the Branchless FGF induces secondary branching by activating the Breathless FGF receptor near the tips of growing primary branches. In sprouty mutants, the FGF pathway is overactive and ectopic branches are induced on the stalks of primary branches. We show that FGF signaling induces sprouty expression in the nearby tip cells, and sprouty acts nonautonomously and in a competitive fashion to block signaling to the more distant stalk cells. sprouty encodes a novel cysteine-rich protein that defines a new family of putative signaling molecules that may similarly function as FGF antagonists in vertebrate development.
几种生长因子信号通路的拮抗剂通过限制同源诱导因子的作用范围，在发育模式形成中发挥重要作用。在此，我们描述了一种果蝇气道顶端分支模式形成过程中的FGF信号拮抗剂。在野生型胚胎中，无分支FGF通过激活正在生长的初级分支尖端附近的呼吸FGF受体来诱导次级分支。在芽生蛋白突变体中，FGF信号通路过度活跃，初级分支的茎干上会诱导出异位分支。我们发现，FGF信号在附近的尖端细胞中诱导芽生蛋白表达，而芽生蛋白以非自主且竞争性的方式发挥作用，阻止信号传递至更远的茎干细胞。芽生蛋白编码一种新型富含半胱氨酸的蛋白质，它定义了一个新的假定信号分子家族，这些分子在脊椎动物发育中可能同样作为FGF拮抗剂发挥作用。
