Cell polarity and morphogenesis in Xenopus embryos

爪蟾胚胎的细胞极性和形态发生

• 批准号: 10406539
• 负责人: Sergei Sokol
• 金额: $ 48.12万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10406539
• 关键词: Actomyosin; Biochemical; Biological; Birth; Cell Polarity; Cell Shape; Cells; Cilia; Congenital Abnormality; Cues; Development; Developmental Process; Disease; Disseminated Malignant Neoplasm; Drosophila genus; Embryo; Epithelial; Event; Experimental Models; Genes; Genetic study; Health; Human; Knowledge; Left; Link; Metastatic to; Molecular; Morphogenesis; Movement; Myosin Type II; Neural Tube Closure; Pathway interactions; Pattern; Polycystic Kidney Diseases; Positioning Attribute; Prevention; Proteins; Proteomics; Renal carcinoma; Signal Pathway; Signal Transduction; Syndrome; System; Systems Biology; Techniques; Tissues; Translating; Vertebrates; Xenopus; cell behavior; cell motility; experience; gastrulation; high resolution imaging; mechanical force; planar cell polarity; polarized cell; programs; protein complex; response; transcriptomics; vertebrate embryos; Actomyosin; Biochemical; Biological; Birth; Cell Polarity; Cell Shape; Cells; Cilia; Congenital Abnormality; Cues; Development; Developmental Process; Disease; Disseminated Malignant Neoplasm; Drosophila genus; Embryo; Epithelial; Event; Experimental Models; Genes; Genetic study; Health; Human; Knowledge; Left; Link; Metastatic to; Molecular; Morphogenesis; Movement; Myosin Type II; Neural Tube Closure; Pathway interactions; Pattern; Polycystic Kidney Diseases; Positioning Attribute; Prevention; Proteins; Proteomics; Renal carcinoma; Signal Pathway; Signal Transduction; Syndrome; System; Systems Biology; Techniques; Tissues; Translating; Vertebrates; Xenopus; cell behavior; cell motility; experience; gastrulation; high resolution imaging; mechanical force; planar cell polarity; polarized cell; programs; protein complex; response; transcriptomics; vertebrate embryos

Project summary In the early vertebrate embryo, signaling pathways instruct cell fates and orchestrate morphogenetic movements, placing cells into proper positions to experience new rounds of signaling and new waves of fate specification and morphogenesis. A long standing question remains how changes in cell polarity determine collective cell behaviors during early development. To approach this problem, this program focuses on the core planar cell polarity (PCP) pathway that is one of the main drivers of morphogenetic processes in vertebrates. Core PCP proteins have been discovered in Drosophila genetic studies. In vertebrates, the PCP protein complexes Vangl/Pk/Celsr and Fz/Dvl/Celsr are conserved and accumulate at opposite cell edges along the body axis, marking tissue polarity. The significance of the core PCP proteins extends far beyond being epithelial polarity markers, as their vertebrate homologs function in key developmental processes, including gastrulation movements, neural tube closure and branching morphogenesis, the formation of functional cilia and left-right patterning. To gain mechanistic knowledge of morphogenetic events, including vertebrate gastrulation, we will study the following long-standing questions in the field: a) how cells polarize in response to a cue, b) how the cell polarity translates into spatially restricted activation of effectors such as Myosin II, and c) how actomyosin contractions and the resulting mechanical forces alter cell shape and coordinate collective cell movements. New force-dependent genes that are involved in the control of morphogenesis will be identified. These directions will be pursued using high resolution imaging, embryological and molecular biological techniques combined with systems level analysis (proteomics and transcriptomics). Our studies will use Xenopus embryos as our main experimental model, due to their fast external development, ease of experimental manipulation and large size allowing biochemical and systems biology approaches. The proposed studies will advance the knowledge of basic cell biological mechanisms underlying vertebrate morphogenesis. High relevance to human health is due to the known connections of PCP signaling to multiple congenital defects and syndromes, polycystic kidney disease and cancers.

项目摘要 在早期的脊椎动物胚胎中，信号通路指导细胞命运和编排 形态发生运动，将细胞置于适当的位置以体验新的回合 信号传导和新的命运规格和形态发生波。一个长期的问题 仍然是细胞极性变化在早期发育过程中决定集体细胞行为的方式。 为了解决此问题，该程序重点介绍核心平面细胞极性（PCP）途径 是脊椎动物形态发生过程的主要驱动因素之一。核心PCP蛋白具有 在果蝇遗传研究中发现。在脊椎动物中，PCP蛋白质复合物 vangl/pk/celsr和fz/dvl/celsr是保守的，沿着相反的单元边缘积聚 体轴，标记组织极性。核心PCP蛋白的意义远远超出 是上皮极性标记，因为它们的脊椎动物同源物在关键发育中起作用 过程，包括胃运动，神经管闭合和分支形态发生， 功能性纤毛和左右图案的形成。获得机械知识 形态发生的事件，包括脊椎动物胃结构，我们将研究以下长期存在 现场中的问题：a）细胞如何响应提示，b）细胞极性如何翻译 进入肌球蛋白II等效应子的空间限制激活，c）肌动蛋白收缩如何 所得的机械力改变了细胞形状并协调集体细胞的运动。 将鉴定出与形态发生有关的新力依赖性基因。 这些方向将使用高分辨率成像，胚胎学和分子来追踪 生物技术结合系统水平分析（蛋白质组学和转录组学）。我们的 由于其快速外部 开发，易于实验操作和大尺寸，允许生化和系统 生物学方法。拟议的研究将提高基本细胞生物学的知识 脊椎动物形态发生的机制。与人类健康的高度相关是由于 PCP信号与多个先天性缺陷和综合症的已知连接，多囊 肾脏疾病和癌症。