Stultz Brian G, Ray Robert P, Hursh Deborah A
Division of Cell and Gene Therapy, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Genesis. 2005 Jul;42(3):181-92. doi: 10.1002/gene.20134.
In mammals, the Transforming Growth Factor-beta (TGF-beta) superfamily controls a variety of developmental processes. In Drosophila, by contrast, a single member of the superfamily, decapentaplegic (dpp) performs most TGF-beta developmental functions. The complexity of dpp functions is reflected in the complex cis-regulatory sequences that flank the gene. Dpp is divided into three regions: Hin, including the protein-coding exons; disk, including 3' cis-regulatory sequences; and shortvein (shv), including noncoding exons and 5' cis-regulatory sequences. We analyzed the cis-regulatory structure of the shortvein region using a nested series of rearrangement breakpoints and rescue constructs. We delimit the molecular regions responsible for three mutant phenotypes: larval lethality, wing venation defects, and head capsule defects. Multiple overlapping elements are responsible for larval lethality and wing venation defects. However, the area regulating head capsule formation is distinct, and resides 5' to these elements. We have demonstrated this by isolating and describing two novel dpp alleles, which affect only the adult head capsule.
在哺乳动物中,转化生长因子-β(TGF-β)超家族控制着多种发育过程。相比之下,在果蝇中,该超家族的单个成员——果蝇的一种基因(dpp)执行了大多数TGF-β的发育功能。dpp功能的复杂性反映在该基因两侧复杂的顺式调控序列中。dpp分为三个区域:Hin,包括蛋白质编码外显子;disk,包括3'顺式调控序列;以及shortvein(shv),包括非编码外显子和5'顺式调控序列。我们使用一系列嵌套的重排断点和拯救构建体分析了shortvein区域的顺式调控结构。我们确定了导致三种突变表型的分子区域:幼虫致死率、翅脉缺陷和头壳缺陷。多个重叠元件导致幼虫致死率和翅脉缺陷。然而,调节头壳形成的区域是不同的,位于这些元件的5'端。我们通过分离和描述两个仅影响成虫头壳的新型dpp等位基因证明了这一点。