Exploration of the Role of Porcupine in Chick Neural Development

豪猪在雏鸡神经发育中的作用探讨

• 批准号: 8858840
• 负责人: Laura W. Burrus
• 金额: $ 1万
• 依托单位: SAN FRANCISCO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8858840
• 关键词: Adult; Affect; Apoptosis; Binding; Biological Assay; Biological Models; Brain; Cancer Model; Cell Polarity; Cell Surface Receptors; Congenital Abnormality; Data; Defect; Development; Dorsal; Embryonic Development; Focal Dermal Hypoplasia; Future; Goals; Homeostasis; Human; Interneurons; L Cells; Lead; Ligands; Link; Lipids; Mediating; Membrane; Methods; Modification; Molecular; Morphogenesis; Motor; Mutation; Neural Tube Closure; Neural Tube Defects; Neural Tube Development; Neural tube; Neurologic; Neurons; Pathway interactions; Patients; Pattern; Phase; Physiological; Play; Population; Porcupines; Positioning Attribute; Post-Translational Protein Processing; Process; Production; Reflex action; Regulation; Research Design; Research Personnel; Role; Sensory; Signal Pathway; Signal Transduction; Specificity; Spinal Cord; Spinal Dysraphism; Staging; Students; Study models; Syndrome; System; Testing; Therapeutic; Thinking; Tissues; Transferase; Wnt proteins; Work; adduct; base; in vivo; in vivo Model; insight; mouse model; neural plate; neurodevelopment; novel; receptor; research study; transmission process; undergraduate student

DESCRIPTION (provided by applicant): As neural tube defects are amongst the most common birth defects, it is vitally important to understand the molecular mechanisms underlying neural tube development. Wnt signaling pathways have well-documented roles in neural tube closure and patterning/expansion of the dorsal spinal cord; however, little is known about how upstream regulators of Wnts affect neural tube development. Porcupine (Porcn) is an important upstream regulator of Wnt ligands and has been linked to neural tube defects in patients with Focal Dermal Hypoplasia. Porcn has a demonstrated role in the lipid modification of Wnt ligands, a post-translational modification that affects their activity and distribution. The objectve of the proposed work is to define the developmental role of Porcn in two distinct stages of neural tube development while assaying the specific roles of Porcn in downstream Wnt signaling pathways, using the chick neural tube as an in vivo model system. To attain the objective of this proposal, we plan to test our central hypothesis that Porcn regulates the closure of the neural tube and for the expansion and patterning of the dorsal spinal cord via b-catenin-dependent Wnt signaling.

描述（由申请人提供）：由于神经管缺陷是最常见的出生缺陷之一，因此了解神经管发育的分子机制至关重要。Wnt信号通路在神经管闭合和脊髓背侧的图案化/扩张中具有良好的记录作用;然而，关于Wnt的上游调节剂如何影响神经管发育知之甚少。豪猪（Porcn）是Wnt配体的重要上游调节因子，与局灶性真皮发育不良患者的神经管缺陷有关。Porcn在Wnt配体的脂质修饰中具有已证实的作用，这是一种影响其活性和分布的翻译后修饰。本研究的目的是以鸡神经管为体内模型系统，研究Porcn在神经管发育的两个不同阶段中的发育作用，同时分析Porcn在下游Wnt信号通路中的特异性作用。为了实现这一建议的目标，我们计划测试我们的中心假设，Porcn调节神经管的关闭，并通过b-连环蛋白依赖的Wnt信号传导的背侧脊髓的扩张和图案化。