Regulation of hedgehog signalling through intracellular trafficking events

刺猬信号级联在胚胎发育过程中几乎形成身体的每一个器官都发挥着作用。在胚胎发育过程中，这一通路关键成员的功能受到干扰，往往会导致子宫内死亡或严重的儿童畸形。此外，对这一途径的破坏也会导致一系列癌症，最值得注意的是极其常见的皮肤癌基底细胞癌。在这项提案中，我们的目标是详细调查的监管机制，运作，以确保这一复杂的相互作用的分子在胚胎发育过程中正确的功能。通过了解这种调节是如何发生的，我们将获得有价值的见解，如何破坏这一途径导致这样一系列的疾病，以及如何调节这一途径的药物可能在治疗环境中发挥作用。

The hedgehog signalling cascade plays a role in forming almost every organ of the body during development of an embryo. Perturbation of the function of key members of this pathway during embryonic development often results in death in utero or severe childhood abnormalities. In addition, disruption to this pathway also results in a range of cancers, most notably the extremely common skin cancer basal cell carcinoma. In this proposal we aim to investigate in detail the regulatory mechanisms which operate to ensure that this complex pathway of interacting molecules functions correctly during embryonic development. By understanding how this regulation occurs we will gain valuable insight into how disruption of this pathway results in such a range of disease, as well as into how agents which modulate this pathway may potentially act in a therapeutic setting.