Department of Biology, Duke University, Durham, North Carolina.
Mol Reprod Dev. 2013 Nov;80(11):882-94. doi: 10.1002/mrd.22228. Epub 2013 Sep 18.
Wnt signaling generates pattern in all animal embryos, from flies and worms to humans, and promotes the undifferentiated, proliferative state critical for stem cells in adult tissues. Inappropriate Wnt pathway activation is the major cause of colorectal cancers, a leading cause of cancer death in humans. Although this pathway has been studied extensively for years, large gaps remain in our understanding of how it switches on and off, and how its activation changes cellular behaviors. Much of what is known about the pathway comes from genetic studies in Drosophila, where a single Wnt molecule, encoded by wingless (wg), directs an array of cell-fate decisions similar to those made by the combined activities of all 19 Wnt family members in vertebrates. Although Wg specifies fate in many tissues, including the brain, limbs, and major organs, the fly embryonic epidermis has proven to be a very powerful system for dissecting pathway activity. It is a simple, accessible tissue, with a pattern that is highly sensitive to small changes in Wg pathway activity. This review discusses what we have learned about Wnt signaling from studying mutations that disrupt epidermal pattern in the fly embryo, highlights recent advances and controversies in the field, and sets these issues in the context of questions that remain about how this essential signaling pathway functions.
Wnt 信号在所有动物胚胎中产生模式，从苍蝇和蠕虫到人，并促进未分化、增殖状态，这对成人组织中的干细胞至关重要。Wnt 途径的异常激活是结直肠癌的主要原因，结直肠癌是人类癌症死亡的主要原因。尽管多年来人们对该途径进行了广泛研究，但我们对其如何开启和关闭以及其激活如何改变细胞行为仍存在很大的理解差距。该途径的大部分知识来自于果蝇的遗传研究，在果蝇中，单个 Wnt 分子，由无翅（wg）编码，指导一系列类似于脊椎动物中所有 19 个 Wnt 家族成员的组合活性所做出的细胞命运决定。尽管 Wg 在许多组织中指定命运，包括大脑、四肢和主要器官，但蝇胚胎表皮已被证明是一个非常强大的系统，可以剖析途径活性。它是一种简单、易于接近的组织，其模式对 Wg 途径活性的微小变化高度敏感。这篇综述讨论了我们从研究破坏蝇胚胎表皮模式的突变中了解到的 Wnt 信号，突出了该领域的最新进展和争议，并将这些问题置于有关这个基本信号途径如何发挥作用的问题背景下。
