Molecular Regulatory Mechanism of Cranial Neural Crest Development

颅神经嵴发育的分子调控机制

基本信息

批准号：
10521267
负责人：
Jun Wang
金额：
$ 37.05万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
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：
2019-12-01 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10521267
关键词：
ATAC-seq Adipocytes Affect Biological Assay Calvaria Cartilage Cell Differentiation process Cells Cephalic Chondrocytes Chondrogenesis Chromatin Complex Congenital Abnormality Connective Tissue Craniofacial Abnormalities Craniosynostosis Cre driver Data Defect Development Differentiation Antigens Disease Embryo Exhibits FOXC1 gene Family Gene Expression Genes Genetic Goals Heart Heterozygote High-Throughput Nucleotide Sequencing Human In Vitro Knowledge Life Ligands Mandible Migration Assay Molecular Morphology Mus Mutant Strains Mice Neural Crest Neural Crest Cell Neuroglia Neurons Organ Osteoblasts Pathway interactions Patients Phase Phosphorylation Phosphotransferases Play Proliferating Protein Array Repression Role Signal Pathway Signal Transduction Smooth Muscle Syndrome Testing Time Tissues Transcription Coactivator Transposase WNT Signaling Pathway antagonist beta catenin bone cell motility cell type chromatin immunoprecipitation cleft lip and palate comparison control conditional knockout craniofacial craniofacial development craniofacial structure craniofacial tissue diagnostic tool genome-wide in vivo in vivo imaging insight knock-down melanocyte migration molecular phenotype multipotent cell mutant novel novel diagnostics novel therapeutic intervention novel therapeutics osteoblast differentiation postnatal protein protein interaction response tool transcription factor transcriptome sequencing

项目摘要

Abstract The cranial neural crest (CNC) cells, the migrating multipotent cells giving rise to different derivatives composing the majority of the craniofacial structures including bone, cartilage, neurons, glia, smooth muscle, melanocytes and adipocytes. Abnormal CNC development results in the most common congenital human birth defects like cleft lip/palate, craniosynostosis, and genetic syndromes, giving a large impact of the life of patients and their families. Therefore, the objective of our proposed study is to understand the molecular regulatory mechanism regulating CNC development. Key Hippo signaling roles have been broadly observed in development and diseases involving many different tissues and organs. However, Hippo's role in craniofacial development is still poorly understood. Wnt signaling is known to play a pivotal role in CNC development and cross talks with Hippo signaling in some context like in heart, whereas there is a knowledge gap of Hippo and Wnt interaction in craniofacial development. We have obtained promising preliminary data indicate that Hippo signaling interacts with Wnt signaling and plays a critical role in regulating CNC-derived craniofacial development. In this proposed study, we will dissect the important roles of Hippo-Yap pathway in CNC cells migration and differentiation, and how Hippo and Wnt pathways cross talk to regulate CNC derived craniofacial development. The goal of the proposed studies is to elucidate the molecular regulatory mechanisms underlying CNC development and help to develop novel therapeutic strategies and diagnostic tools for craniofacial defects.

抽象的颅神经嵴（CNC）细胞，即迁移的多能细胞，产生不同的构成大部分颅面结构的衍生物，包括骨、软骨、神经元、神经胶质细胞、平滑肌、黑素细胞和脂肪细胞。 CNC开发结果异常最常见的先天性人类出生缺陷，如唇裂/腭裂、颅缝早闭和遗传综合症，给患者及其家人的生活带来很大影响。因此，我们提出的研究的目的是了解调节的分子调节机制数控开发。 Hippo 信号传导的关键作用在发育和发育过程中已被广泛观察到。涉及许多不同组织和器官的疾病。然而，河马在颅面部的作用发展仍然知之甚少。众所周知，Wnt 信号在 CNC 中发挥着关键作用在某些情况下，比如在心里，与河马信号的发展和交叉对话，而有 Hippo 和 Wnt 在颅面发育中相互作用的知识差距。我们已经获得了有希望的初步数据表明，Hippo 信号与 Wnt 信号相互作用，并发挥着重要作用在调节 CNC 衍生的颅面发育中发挥着关键作用。在这项拟议的研究中，我们将剖析 Hippo-Yap 通路在 CNC 细胞迁移和分化中的重要作用，以及 Hippo 和 Wnt 通路如何相互作用来调节 CNC 衍生的颅面发育。这拟议研究的目标是阐明 CNC 背后的分子调控机制开发并帮助开发颅面部的新治疗策略和诊断工具缺陷。