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刺猬信号通路和果蝇背腹轴决定基因活性对果蝇翅膀图案形成的定量影响。

Quantitative effects of hedgehog and decapentaplegic activity on the patterning of the Drosophila wing.

作者信息

Ingham P W, Fietz M J

机构信息

Molecular Embryology Laboratory, Imperial Cancer Research Fund, London, UK.

出版信息

Curr Biol. 1995 Apr 1;5(4):432-40. doi: 10.1016/s0960-9822(95)00084-4.

Abstract

BACKGROUND

Members of the hedgehog (hh) gene family encode a novel class of proteins implicated in positional signalling in both invertebrates and vertebrates. In Drosophila, the hh gene has been shown to regulate patterning of the imaginal discs, the precursors of the insect limbs. In a remarkably similar fashion, the function and expression of the sonic hedgehog (shh) gene is closely associated with the 'zone of polarizing activity' (ZPA) that controls antero-posterior patterning of the vertebrate limb. Both of these functions suggest a role for hedgehog family proteins as morphogens. An alternative possibility, however, is that hh and its homologues act to control the expression of other instructive signalling molecules.

RESULTS

We have explored this issue by examining the effects on Drosophila wing patterning of ectopically expressing varying levels of hh and shh, as well as of the putative hh target gene, decapentaplegic (dpp), a member of the transforming growth factor-beta family of signalling molecules. We find that different levels of hh activity can induce graded changes in the patterning of the wing, and that zebrafish shh acts in a similar though attenuated fashion. Varying levels of ectopic hh and shh activity can differentially activate transcription of the patched and dpp genes. Furthermore, ectopic expression of dpp alone is sufficient to induce the pattern alterations caused by ectopic hh or shh activity.

CONCLUSION

Thus, hh family proteins can elicit different responses in a dose-dependent manner in the imaginal disc. The principal function of hh, however, is to activate transcription of dpp at the compartment boundary, thereby establishing a source of dpp activity that is the primary determinant of antero-posterior patterning.

摘要

背景

刺猬(hh)基因家族的成员编码一类新型蛋白质,这类蛋白质在无脊椎动物和脊椎动物的位置信号传导中均有涉及。在果蝇中,hh基因已被证明可调节成虫盘(昆虫肢体的前体)的模式形成。以一种非常相似的方式,音猬因子(shh)基因的功能和表达与控制脊椎动物肢体前后模式形成的“极化活性区”(ZPA)密切相关。这两种功能都表明刺猬家族蛋白作为形态发生素发挥作用。然而,另一种可能性是hh及其同源物起到控制其他指导性信号分子表达的作用。

结果

我们通过检查异位表达不同水平的hh和shh以及假定的hh靶基因——脱磷酸化蛋白(dpp,一种转化生长因子-β信号分子家族的成员)对果蝇翅膀模式形成的影响来探讨这个问题。我们发现不同水平的hh活性可诱导翅膀模式形成的分级变化,并且斑马鱼shh以类似但减弱的方式起作用。不同水平的异位hh和shh活性可差异激活patched和dpp基因的转录。此外,单独异位表达dpp足以诱导由异位hh或shh活性引起的模式改变。

结论

因此,hh家族蛋白可在成虫盘中以剂量依赖的方式引发不同的反应。然而,hh的主要功能是在隔室边界激活dpp的转录,从而建立dpp活性的来源,这是前后模式形成的主要决定因素。

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