Wharton K, Ray R P, Findley S D, Duncan H E, Gelbart W M
Department of Cellular and Developmental Biology, Harvard University, Cambridge, Massachusetts 02138, USA. kristi_wharton/brown.edu
Genetics. 1996 Feb;142(2):493-505. doi: 10.1093/genetics/142.2.493.
We have identified the molecular lesions associated with six point mutations in the Drosophila TGF-beta homologue decapentaplegic (dpp). The sites of these mutations define residues within both the pro and ligand regions that are essential for dpp function in vivo. While all of these mutations affect residues that are highly conserved among TGF-beta superfamily members, the phenotypic consequences of the different alleles are quite distinct. Through an analysis of these mutant phenotypes, both in cuticle preparations and with molecular probes, we have assessed the functional significance of specific residues that are conserved among the different members of the superfamily. In addition, we have tested for conditional genetic interactions between the different alleles. We show that two of the alleles are temperature sensitive for the embryonic functions of dpp, such that these alleles are not only embryonic viable as homozygotes but also partially complement other dpp hypomorphs at low temperatures. Our results are discussed with regard to in vitro mutagenesis data on other TGF-beta-like molecules, as well as with regard to the regulation of dpp cell signaling in Drosophila.
我们已经鉴定出与果蝇转化生长因子β（TGF-β）同源物“十体不全”（dpp）中的六个点突变相关的分子损伤。这些突变位点确定了前体区域和配体区域内对于dpp在体内功能至关重要的残基。虽然所有这些突变都影响TGF-β超家族成员中高度保守的残基，但不同等位基因的表型后果却截然不同。通过对这些突变体表型的分析，包括在表皮制备物中以及使用分子探针进行分析，我们评估了超家族不同成员中保守的特定残基的功能重要性。此外，我们还测试了不同等位基因之间的条件性遗传相互作用。我们发现其中两个等位基因对dpp的胚胎功能具有温度敏感性，以至于这些等位基因作为纯合子不仅在胚胎期存活，而且在低温下还能部分互补其他dpp亚效等位基因。我们将结合关于其他TGF-β样分子的体外诱变数据以及果蝇中dpp细胞信号传导的调控来讨论我们的结果。
