Padgett R W, Wozney J M, Gelbart W M
Department of Cellular and Developmental Biology, Harvard University, Cambridge, MA 02138-2097.
Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2905-9. doi: 10.1073/pnas.90.7.2905.
The type beta transforming growth factor family is composed of a series of processed, secreted growth factors, several of which have been implicated in important regulatory roles in cell determination, inductive interactions, and tissue differentiation. Among these factors, the sequence of the DPP protein from Drosophila is most similar to two of the vertebrate bone morphogenetic proteins, BMP2 and BMP4. Here we report that the human BMP4 ligand sequences can function in lieu of DPP in Drosophila embryos. We introduced the ligand region from human BMP4 into a genomic fragment of the dpp gene in place of the Drosophila ligand sequences and recovered transgenic flies by P-element transformation. We find that this chimeric dpp-BMP4 transgene can completely rescue the embryonic dorsal-ventral patterning defect of null dpp mutant genotypes. We infer that the chimeric DPP-BMP4 protein can be processed properly and, by analogy with the action of other family members, can activate the endogenous DPP receptor to carry out the events necessary for dorsal-ventral patterning. Our evidence suggests that the DPP-BMP4 signal transduction pathway has been functionally conserved for at least 600 million years.
β型转化生长因子家族由一系列经过加工、分泌的生长因子组成,其中几种在细胞决定、诱导性相互作用和组织分化中发挥重要调节作用。在这些因子中,果蝇的DPP蛋白序列与脊椎动物的两种骨形态发生蛋白BMP2和BMP4最为相似。在此我们报告,人BMP4配体序列在果蝇胚胎中可替代DPP发挥作用。我们将人BMP4的配体区域导入dpp基因的基因组片段中,取代果蝇的配体序列,并通过P因子转化获得转基因果蝇。我们发现,这种嵌合的dpp - BMP4转基因能够完全挽救无效dpp突变基因型的胚胎背腹模式缺陷。我们推断,嵌合的DPP - BMP4蛋白能够被正确加工,并且类似于其他家族成员的作用,能够激活内源性DPP受体以执行背腹模式形成所需的事件。我们的证据表明,DPP - BMP4信号转导途径在功能上至少保守了6亿年。