Siegfried E, Perrimon N
Department of Genetics, Harvard Medical School, Boston, MA 02115.
Bioessays. 1994 Jun;16(6):395-404. doi: 10.1002/bies.950160607.
The link between oncogenesis and normal development is well illustrated by the study of the Wnt family of proteins. The first Wnt gene (int-1) was identified over a decade ago as a proto-oncogene, activated in response to proviral insertion of a mouse mammary tumor virus. Subsequently, the discovery that Drosophila wingless, a developmentally important gene, is homologous to int-1 supported the notion that int-1 may have a role in normal development. In the last few years it has been recognized that int-1 and Wingless belong to a large family of related glyco-proteins found in vertebrates and invertebrates. In recognition of this, members of this family have been renamed Wnts, an amalgam of int and Wingless. Investigation of Wnt genes in Xenopus and mouse indicates that Wnts have a role in cell proliferation, differentiation and body axis formation. Further analysis in Drosophila has revealed that Wingless function is required in several developmental processes in the embryo and imaginal discs. In addition, a genetic approach has identified some of the molecules required for the transmission and reception of the Wingless signal. We will review recent data which have contributed to our growing understanding of the function and mechanism of Drosophila Wingless signaling in cell fate determination, growth and specification of pattern.
对Wnt蛋白家族的研究很好地阐释了肿瘤发生与正常发育之间的联系。首个Wnt基因(int-1)在十多年前被鉴定为原癌基因,它因小鼠乳腺肿瘤病毒的前病毒插入而激活。随后,果蝇无翅基因(一种对发育很重要的基因)与int-1同源这一发现支持了int-1可能在正常发育中起作用的观点。在过去几年里,人们认识到int-1和无翅基因属于在脊椎动物和无脊椎动物中发现的一个大型相关糖蛋白家族。鉴于此,该家族成员被重新命名为Wnts,是int和无翅的合成词。对非洲爪蟾和小鼠中Wnt基因的研究表明,Wnts在细胞增殖、分化和体轴形成中起作用。在果蝇中的进一步分析揭示,无翅基因的功能在胚胎和成虫盘的几个发育过程中是必需的。此外,一种遗传学方法已经确定了无翅信号传递和接收所需的一些分子。我们将综述最近的数据,这些数据有助于我们进一步了解果蝇无翅信号在细胞命运决定、生长和模式特化中的功能和机制。