Molecular Regulatory Mechanism of Cranial Neural Crest Development

摘要 颅神经脊细胞，迁移的多能细胞产生不同的 构成头面部主要结构的衍生物，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。不正常的数控开发结果 在人类最常见的先天性出生缺陷中，如唇腭裂、颅缝早闭和 遗传综合征，给患者及其家人的生活带来很大影响。因此， 我们建议的研究目的是了解分子调控机制 数控技术的发展。河马的关键信号作用在发育和发育过程中被广泛观察到 涉及许多不同组织和器官的疾病。然而，河马在头面部的作用 人们对发展仍然知之甚少。众所周知，WNT信号在cnc中起着关键作用。 在某些情况下，例如在内心，开发和与河马信号的交叉对话，而 河马和Wnt在头面部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，河马信号与Wnt信号相互作用，并发挥作用 在调节计算机数控系统衍生的颅面发育中的关键作用。在这项拟议的研究中，我们将 剖析HIPPO-YAP通路在数控细胞迁移和分化中的重要作用 河马和Wnt通路如何相互作用来调节cnc衍生的颅面发育。这个 拟议研究的目标是阐明计算机数控系统背后的分子调控机制 开发和帮助开发新的颅面治疗策略和诊断工具 缺陷。

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.