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Defining the relationship of ciliary Arl13b and Smoothened

定义睫状 Arl13b 和 Smoothened 的关系

基本信息

批准号：
9977000
负责人：
Eduardo D. Gigante
金额：
$ 4.55万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-15 至 2021-06-01
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9977000
关键词：
Affect Alleles Binding Biological Assay Brain Cilia Complex Congenital Abnormality Data Development Digit structure Disease Embryo Embryonic Development Engineering Erinaceidae Exencephalies Face G-Protein-Coupled Receptors GTP-Binding Protein alpha Subunits, Gs GTP-Binding Proteins Genetic Genetic Transcription Guanosine Triphosphate Phosphohydrolases Hand Holoprosencephaly Joubert syndrome Knowledge Lead Ligands Limb structure Link Malignant Neoplasms Measures Methods Modeling Mus Mutant Strains Mice Mutation Neural tube Organelles Pathway interactions Pattern Phenotype Physiological Point Mutation Positioning Attribute Pregnancy Process Proteins Publishing Regulation Research Role SHH gene Severities Signal Pathway Signal Transduction Skeleton Sonic Hedgehog Pathway Spinal Cord Spinal Dysraphism Testing Time Training Transducers base bone ciliopathy experimental study improved inhibitor/antagonist knock-down neural patterning neurodevelopment novel response smoothened signaling pathway tool transcription factor

项目摘要

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.

项目总结