Hoffmann F M
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706.
Mol Reprod Dev. 1992 Jun;32(2):173-8. doi: 10.1002/mrd.1080320214.
Many Drosophila genes have now been identified with substantial sequence similarity to vertebrate protooncogenes and growth factors. Some of these have been isolated directly by cross-hybridization with vertebrate probes and some have been recognized in the sequences of genes cloned because of their intiguing mutant phenotypes. An example of a gene isolated for its interesting development functions but with homology to a vertebrate growth factor is the Drosophila decapentaplegic gene (dpp). An example of a Drosophila gene isolated by virtue of its sequence conservation is the vgr/60A gene. Both dpp and vgr/60A are members of the transforming growth factor-beta family and are most similar to the human bone morphogenetic proteins. The regulation of the dpp gene by several different groups of pattern formation genes including the dorsal/ventral group, the terminal group, the segment polarity genes, and the homeotic genes indicates that many events in embryogenesis require the cell to cell communication mediated by the secreted dpp protein. The temporal and spatial pattern of vgr/60A expression differs from that of dpp indicating that it may be regulated by different pattern information genes. The experimental advantages of the Drosophila system should permit a better understanding of the importance of growth factor homologs in specific developmental events, aid in establishing the functional interactions between these regulatory molecules, and identify new genes that are important for the biological functions of growth factors. It is likely that some of the newly identified genes will have vertebrate homologs and the analysis of these may be helpful in studies on vertebrate development and tumor biology.
现在已鉴定出许多果蝇基因与脊椎动物原癌基因和生长因子具有显著的序列相似性。其中一些是通过与脊椎动物探针交叉杂交直接分离得到的,还有一些是由于其有趣的突变表型而在克隆基因的序列中被识别出来的。一个因其有趣的发育功能而被分离出来且与脊椎动物生长因子具有同源性的基因例子是果蝇的“五体不全”基因(dpp)。一个凭借其序列保守性而被分离出来的果蝇基因例子是vgr/60A基因。dpp和vgr/60A都是转化生长因子-β家族的成员,并且与人类骨形态发生蛋白最为相似。包括背腹组、末端组、体节极性基因和同源异型基因在内的几组不同的模式形成基因对dpp基因的调控表明,胚胎发育中的许多事件都需要由分泌的dpp蛋白介导的细胞间通讯。vgr/60A表达的时空模式与dpp不同,这表明它可能受不同的模式信息基因调控。果蝇系统的实验优势应该有助于更好地理解生长因子同源物在特定发育事件中的重要性,有助于确定这些调控分子之间的功能相互作用,并鉴定出对生长因子生物学功能很重要的新基因。很可能一些新鉴定出的基因会有脊椎动物同源物,对它们的分析可能有助于脊椎动物发育和肿瘤生物学的研究。