Hartl Tom A, Scott Matthew P
Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA.
Methods. 2014 Jun 15;68(1):199-206. doi: 10.1016/j.ymeth.2014.02.002. Epub 2014 Feb 17.
Hedgehog (Hh) signal transduction is necessary for the development of most mammalian tissues and can go awry and cause birth defects or cancer. Hh signaling was initially described in Drosophila, and much of what we know today about mammalian Hh signaling was directly guided by discoveries in the fly. Indeed, Hh signaling is a wonderful example of the use of non-vertebrate model organisms to make basic discoveries that lead to new disease treatment. The first pharmaceutical to treat hyperactive Hh signaling in Basal Cell Carcinoma was released in 2012, approximately 30 years after the isolation of Hh mutants in Drosophila. The study of Hh signaling has been greatly facilitated by the imaginal wing disc, a tissue with terrific experimental advantages. Studies using the wing disc have led to an understanding of Hh ligand processing, packaging into particles for transmission, secretion, reception, signal transduction, target gene activation, and tissue patterning. Here we describe the imaginal wing disc, how Hh patterns this tissue, and provide methods to use wing discs to study Hh signaling in Drosophila. The tools and approaches we highlight form the cornerstone of research efforts in many laboratories that use Drosophila to study Hh signaling, and are essential for ongoing discoveries.
刺猬信号通路(Hh)的转导对于大多数哺乳动物组织的发育是必需的,该通路出现异常时会导致出生缺陷或癌症。Hh信号通路最初是在果蝇中被描述的,如今我们对哺乳动物Hh信号通路的许多了解都直接得益于在果蝇中的发现。事实上,Hh信号通路是利用非脊椎动物模式生物做出基础发现从而带来新疾病治疗方法的一个绝佳例子。在果蝇中分离出Hh突变体约30年后,首款用于治疗基底细胞癌中过度活跃的Hh信号通路的药物于2012年问世。果蝇的成虫翅芽是一种具有诸多实验优势的组织,极大地推动了对Hh信号通路的研究。利用翅芽进行的研究使人们了解了Hh配体的加工、包装成用于传递的颗粒、分泌、接收、信号转导、靶基因激活以及组织模式形成。在此,我们描述了成虫翅芽、Hh如何塑造该组织,并提供了利用翅芽研究果蝇中Hh信号通路的方法。我们所强调的工具和方法构成了许多利用果蝇研究Hh信号通路的实验室研究工作的基石,对于持续不断的发现至关重要。