ErbB signaling in vertebrate morphogenesis

脊椎动物形态发生中的 ErbB 信号传导

• 批准号: 7915753
• 负责人: CHENBEI CHANG
• 金额: $ 31.17万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7915753
• 关键词: Actins; Address; Adhesions; African; Biological Models; Cadherins; Cell Adhesion; Cell Proliferation; Cell-Cell Adhesion; Cellular Morphology; Complex; Cytoskeleton; DNA Sequence Rearrangement; Data; Development; Disseminated Malignant Neoplasm; Embryo; Embryonic Development; Endoderm; Ensure; Epidermal Growth Factor; Family; Foundations; Goals; Grant; Growth Factor; Guanosine Triphosphate Phosphohydrolases; Heart; Laboratory Study; Ligands; Light; Malignant Neoplasms; Mediating; Mesoderm; Mesoderm Cell; Modification; Molecular; Morphogenesis; Movement; Mutation; Neoplasm Metastasis; Neurites; Neurons; Organ; Pathway interactions; Phosphorylation; Phosphotransferases; Process; Protein Tyrosine Kinase; Rana; Receptor Protein-Tyrosine Kinases; Research; Role; Signal Pathway; Signal Transduction; Tissues; Xenopus; Xenopus laevis; Xenopus sp.; base; cancer cell; cell behavior; cell motility; gastrulation; insight; migration; neurodevelopment; new therapeutic target; receptor; relating to nervous system; rho; rho GTP-Binding Proteins; src-Family Kinases; tumor growth

The overall goal of the proposed research is to understand how ErbB signaling regulates cell adhesion and movements during early vertebrate development. Xenopus gastrulation will be used as the model system in this study. ErbB signaling involves four related receptor tyrosine kinases (ErbBs) that mediate actions of epidermal growth factor (EGF) and its related growth factors. It is best known for its function in cancer, as mutations in both EGF-like ligands and ErbB receptors are implicated in cancer formation and progression. While the roles of ErbB signaling in cell proliferation and tumor growth are well studied, the mechanisms of ErbB signaling in cancer metastasis are less understood. During early vertebrate development, ErbB signaling is known to modulate multiple processes, including heart morphogenesis, neurite extension and neuronal migration. The means via which ErbB signaling controls cell morphology and/or movements in these processes are not comprehended. Preliminary studies from this laboratory demonstrate that in addition to modulate cell behaviors in cancer and in heart and neural development, ErbB signaling also controls cell movements during gastrulation in early frog embryos. Gastrulation is the process through which mesoderm and endoderm are placed inside the embryos to form internal tissues and organs. Coordinated cell movements during this process ensure proper formation of the vertebrate body plan. ErbB signaling regulates gastrulation morphogenesis, but the detailed mechanisms are not understood. This grant is intended to examine the hypothesis that Src and Abl families of tyrosine kinases are activated downstream of ErbB receptors to regulate gastrulation movements via modification of cell adhesion complexes. In aim 1, the roles of these cytoplasmic tyrosine kinase pathways in ErbB-dependent gastrulation movements will be examined. In aim 2, the effects of the ErbB-Src/ErbB-Abl signals on the dynamic organization of actin cytoskeleton will be investigated. Results obtained from these studies will provide crucial insight into the mechanisms via which ErbB signaling controls gastrulation and will help to shed light on how ErbB signaling may modulate cell behaviors in other contexts, such as in cancer metastasis and in cell movements during mammalian embryogenesis.

这项研究的总体目标是了解ErbB信号如何调节细胞粘附， 脊椎动物早期发育过程中的运动。非洲爪蟾原肠胚形成将被用作模型系统， 本研究 ErbB信号转导涉及四种相关的受体酪氨酸激酶（ErbBs），它们介导表皮细胞的作用。 EGF及其相关生长因子它最为人所知的是它在癌症中的功能，因为它在癌症中的突变。 EGF样配体和ErbB受体都与癌症的形成和发展有关。而 ErbB信号传导在细胞增殖和肿瘤生长中的作用已被充分研究，ErbB信号传导的机制 在癌症转移中的信号传导较少被理解。在脊椎动物的早期发育过程中，ErbB信号传导是 已知调节多个过程，包括心脏形态发生、神经突延伸和神经元 迁移ErbB信号传导控制这些细胞中的细胞形态和/或运动的手段， 过程不被理解。 该实验室的初步研究表明，除了调节癌症中的细胞行为外， 在心脏和神经发育中，ErbB信号也控制早期原肠胚形成期间细胞运动， 青蛙胚胎原肠胚形成是中胚层和内胚层被放置在胃内的过程。 胚胎形成内部组织和器官。在此过程中协调细胞运动确保适当的 脊椎动物身体平面的形成。ErbB信号调节原肠胚形态发生，但详细的 机制不被理解。该资助旨在检验Src和Abl家族的假设 酪氨酸激酶在ErbB受体的下游被激活，通过以下途径调节原肠胚形成运动： 细胞粘附复合物的修饰。在aim 1中，这些胞质酪氨酸激酶途径在 将检查ErbB依赖性原肠胚形成运动。在目的2中，ErbB-Src/ErbB-Abl的作用被证实是有效的。 将研究肌动蛋白细胞骨架动态组织的信号。从这些获得的结果 这些研究将为ErbB信号控制原肠胚形成的机制提供重要的见解， 将有助于阐明ErbB信号传导如何在其他情况下调节细胞行为，例如在 癌症转移和哺乳动物胚胎发生过程中的细胞运动。