Defining the relationship of ciliary Arl13b and Smoothened

项目摘要 已知Hedgehog信号通路的突变会导致常见的出生缺陷。在这里，我建议 研究刺猬途径的组成部分是如何由初级纤毛的蛋白质调节的。 我们希望通过研究这些途径的交叉点，我们可以更好地理解这两个过程是如何发生的。 在健康和疾病状态下相互作用。已知Hedgehog信号通路会影响 早期发育的各个方面，包括大脑，脊髓，面部骨骼，四肢和 手奇怪的是，这一途径依赖于一种鲜为人知的细胞器，称为初级纤毛。我 我认为，更好地理解通路功能的关键是研究通路的组成部分如何 由初级纤毛及其纤毛蛋白调节。我假设睫状蛋白Arl13b是 这是完全激活Smoothened所必需的，Smoothened是Hedgehog信号级联的激活剂。具体 该项目的目的是：1）使用新发明的测定方法来测量Smoothened激活， 睫状和非睫状Arl 13 b和2）表征睫状和非睫状Arl 13 b具有的生理影响 在发育中的小鼠胚胎中的平滑激活。通过这些方法，我的目的是定义的作用， Arl13b在Smoothened激活中的作用，并努力更好地理解Hedgehog通路与 初级纤毛

PROJECT SUMMARY Mutations to the Hedgehog signaling pathway are known to cause common birth defects. Here, I propose studying how the components of the Hedgehog pathway are regulated by the proteins of the primary cilium. We hope that by studying where these pathways intersect we can better understand how the two processes interact together in the healthy and disease states. The Hedgehog signaling pathway is known to influence a variety of aspects of early development, including the brain, spinal cord, and skeleton of the face, limbs and hands. Strangely, this pathway relies on a poorly understood cellular organelle called the primary cilium. I propose that the key to better understanding pathway function is my studying how the pathway’s components are regulated by the primary cilium and its ciliary proteins. I have hypothesized that a ciliary protein Arl13b is necessary for the full activation of Smoothened, the activator of the Hedgehog signaling cascade. The specific aims of this project are 1) to use a newly invented assay to measure Smoothened activation in the context of ciliary and non-ciliary Arl13b and 2) to characterize the physiological impact ciliary and non-ciliary Arl13b has on Smoothened activation in the developing mouse embryo. Through these methods, I aim to define the role of Arl13b in Smoothened activation and strive to better understand the link between the Hedgehog pathway and the primary cilium.