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Characterization of the roles and regulation of Draxin in cranial neural crest

Draxin 在颅神经嵴中的作用和调节的表征

基本信息

批准号：
10632334
负责人：
Erica Hutchins
金额：
$ 24.9万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10632334
关键词：
Affect Binding Biochemistry Bioinformatics Biological Assay Cartilage Cell Adhesion Cell Adhesion Molecules Cell-Cell Adhesion Cephalic ChIP-seq Chick Cleft Palate Co-Immunoprecipitations Craniofacial Abnormalities Data Defect Development DiGeorge Syndrome Disease Down-Regulation E-Cadherin Embryo Embryology Etiology Event Extracellular Matrix Proteins Face Fluorescence Resonance Energy Transfer Gelatinase B Gene Expression Genetic Transcription Genomic Segment Goals Head Image Immunoprecipitation In Situ Hybridization Integrins Laminin Lead Ligation Light Maintenance Mandibulofacial Dysostosis Mediating Mentors Messenger RNA Microscopy Molecular Mutate Mutation N-Cadherin Names Neural Crest Neural Crest Cell Neural tube Neuraxis Pathway interactions Phase Play Population Post-Transcriptional Regulation Proteins RNA RNA-Binding Proteins Regulation Reporter Research Role Site Skeleton Tail Techniques Time Translational Research Untranslated Regions Up-Regulation WNT Signaling Pathway antagonist beta catenin craniofacial craniofacial structure epithelial to mesenchymal transition experimental study in vivo knock-down laminin alpha5 mRNA Expression malformation migration neural plate neuroepithelium overexpression public health relevance receptor sensor spatiotemporal stem cell population time use

项目摘要

PROJECT SUMMARY The neural crest (NC) is a stem cell population that originates within the forming central nervous system. NC cells delaminate from the neuroepithelium by undergoing a spatiotemporally regulated epithelial-to- mesenchymal transition (EMT) that proceeds in a coordinated wave head-to-tail to exit from the neural tube. Cranial NC cells, which arise in the head region of the embryo and are the only NC population in vivo with the ability to differentiate into craniofacial skeleton and cartilage, are indispensable for the development of the face; mutations affecting NC development result in numerous diseases and malformations affecting the craniofacial structures (e.g. Treacher Collins syndrome, cleft palate, etc.). Thus, a thorough understanding of the regulation of cranial NC EMT is essential to identify the etiology of craniofacial abnormalities. To date, research has focused on unraveling early events governing cranial NC induction at the neural plate border and the mechanism of delamination from the neural tube. However, little is known about the regulatory changes governing the timing of NC EMT and exit from the neural tube. My preliminary studies demonstrate that a Wnt pathway antagonist, Draxin, plays an important role in controlling the timing of NC EMT, perturbations of which have negative consequences for cranial NC migration. This role for Draxin is particularly interesting in light of the fact that the Wnt signaling pathway has been shown to be a major driver of NC development. The goal of this Proposal is to investigate the molecular mechanism by which Draxin affects cranial NC EMT, with focus on its role in Wnt signaling. To this end, the Specific Aims of this Proposal seek to combine chick embryology with state-of-the-art imaging and biochemistry to: 1) Characterize the interaction of Draxin and Wnt signaling in cranial NC EMT; 2) Identify the role of Draxin in the regulation of cell adhesion proteins; 3) Characterize the post-transcriptional regulation of Draxin; and 4) Identify the role of Draxin in the regulation of extracellular matrix proteins. The results of this Proposal will significantly enhance our understanding of the regulation of cranial NC EMT and migration, providing new scientific avenues for translational research applications in the treatment of craniofacial defects.

项目总结