Finelli A L, Xie T, Bossie C A, Blackman R K, Padgett R W
Waksman Institute, Rutgers University, Piscataway, New Jersey 08855-0758, USA.
Genetics. 1995 Sep;141(1):271-81. doi: 10.1093/genetics/141.1.271.
The Drosophila decapentaplegic (dpp) gene, a member of the transforming growth factor beta superfamily of growth factors, is critical for specification of the embryonic dorsal-ventral axis, for proper formation of the midgut, and for formation of Drosophila adult structures. The Drosophila tolloid gene has been shown to genetically interact with dpp. The genetic interactions between tolloid and dpp suggests a model in which the tolloid protein participates in a complex containing the DPP ligand, its protease serving to activate DPP, either directly or indirectly. We report here the identification and cloning of another Drosophila member of the tolloid/bone morphogenic protein (BMP) 1 family, tolkin, which is located 700 bp 5' to tolloid. Its overall structure is like tolloid, with an N-terminal metalloprotease domain, five complement subcomponents C1r/C1s, Uegf, and Bmp1 (CUB) repeats and two epidermal growth factor (EGF) repeats. Its expression pattern overlaps that of tolloid and dpp in early embryos and diverges in later stages. In larval tissues, both tolloid and tolkin are expressed uniformly in the imaginal disks. In the brain, both tolloid and tolkin are expressed in the outer proliferation center, whereas tolkin has another stripe of expression near the outer proliferation center. Analysis of lethal mutations in tolkin indicate it is vital during larval and pupal stages. Analysis of its mutant phenotypes and expression patterns suggests that its functions may be mostly independent of tolloid and dpp.
果蝇的“十五体瘫”（dpp）基因是转化生长因子β超家族生长因子的成员之一，对胚胎背腹轴的特化、中肠的正常形成以及果蝇成虫结构的形成至关重要。果蝇的类 tolloid 基因已被证明与 dpp 存在遗传相互作用。tolloid 与 dpp 之间的遗传相互作用提示了一种模型，即 tolloid 蛋白参与了一个包含 DPP 配体的复合物，其蛋白酶直接或间接地用于激活 DPP。我们在此报告了 tolloid/骨形态发生蛋白（BMP）1 家族的另一个果蝇成员 tolkin 的鉴定与克隆，它位于 tolloid 基因 5'端 700 bp 处。其整体结构与 tolloid 相似，具有一个 N 端金属蛋白酶结构域、五个补体亚成分 C1r/C1s、Uegf 和 Bmp1（CUB）重复序列以及两个表皮生长因子（EGF）重复序列。它在早期胚胎中的表达模式与 tolloid 和 dpp 的表达模式重叠，而在后期阶段则有所不同。在幼虫组织中，tolloid 和 tolkin 在成虫盘上均呈均匀表达。在大脑中，tolloid 和 tolkin 均在外周增殖中心表达，而 tolkin 在靠近外周增殖中心的位置还有另一条表达带。对 tolkin 致死突变的分析表明它在幼虫和蛹期至关重要。对其突变体表型和表达模式的分析表明，其功能可能大多独立于 tolloid 和 dpp。
