Dynamics of epithelial morphogenesis

上皮形态发生的动力学

• 批准号: 8695795
• 负责人: Stanislav Y. Shvartsman
• 金额: $ 30.48万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8695795
• 关键词: Ablation; Address; Birds; Cell Adhesion Molecules; Cell Death; Cell Shape; Cell division; Cells; Chemicals; Complex; Computer Simulation; DNA Sequence Rearrangement; Development; Dorsal; Drosophila genus; Epithelial; Epithelial Cells; Epithelium; Feedback; Fishes; Fluorescence Resonance Energy Transfer; Genetic; Germ Cells; Goals; Human; Image; Insecta; Lasers; Lead; Life; Light; Maps; Mechanics; Mesoderm; Modeling; Molecular; Morphogenesis; Myosin ATPase; Nature; Neural Tube Closure; Neural Tube Defects; Neuraxis; Oocytes; Oogenesis; Organ; Pattern; Positioning Attribute; Process; Property; Shapes; Signal Transduction; Specific qualifier value; Staging; Structure; System; Testing; Tissues; Transgenic Organisms; Tubular formation; Work; appendage; base; cardiogenesis; cell transformation; computer framework; computer studies; developmental disease; driving force; fly; mutant; neuroepithelium; optic cup; public health relevance; research study; sensor; three dimensional structure; two-dimensional

DESCRIPTION: We propose to combine computational and experimental approaches to investigate the mechanisms of epithelial morphogenesis, defined as the set of processes that transform sheets of cells into three-dimensional (3d) structures of tissues and organs. Studies of epithelial morphogenesis are important for understanding of normal development and for elucidating the origins of developmental abnormalities, such as neural tube defects. We will focus on a type of epithelial morphogenesis that involves only cell shape changes and rearrangements and does not depend on cell divisions or death. Among the examples of this type of morphogenesis are the early stages of heart development in fish, the formation of optic cups in birds, and mesoderm invagination in insects. In our experimental system (Drosophila oogenesis), a sheet of nondividing cells gives rise to an elaborate 3d shape. This transformation is induced by well-understood chemical signals, which specify a fate map, a correspondence between positions of cells within the sheet and their ultimate positions within the 3d structure. Our goal is to understand how the two-dimensional (2d) fate map is transformed into a 3d structure. Answering this question is important in multiple developmental systems, from simple metazoans to humans. Our hypothesis is that 3d epithelial morphogenesis during Drosophila oogenesis is driven by the 2d distribution of mechanical tensions within the patterned cell sheet. We will test this hypothesis by computational modeling and live imaging of epithelial dynamics and by direct analysis of mechanical tensions in patterned epithelial sheets. Our work will lead to an experimentally validated computational framework for 3d epithelial morphogenesis. Given the highly conserved nature of processes involved in epithelial morphogenesis, the results of or studies may shed light on epithelial dynamics in wide range of developmental systems.

描述：我们建议将计算和实验方法结合起来，以研究上皮形态发生的机制，该机理定义为将细胞板转化为组织和器官的三维（3D）结构的过程集。上皮形态发生的研究对于理解正常发育和阐明发育异常的起源（例如神经管缺陷）很重要。我们将专注于一种仅涉及细胞形状变化和重排的上皮形态发生，并且不取决于细胞分裂或死亡。这种形态发生的例子包括鱼类心脏发育的早期阶段，鸟类的视觉杯的形成以及昆虫中的中胚层内陷。在我们的实验系统（果蝇卵子发生）中，一组非分散的细胞产生了精致的3D形状。这种转化是由牢固理解的化学信号引起的，该信号指定了命运图，板块内部位置之间的对应关系及其在3D结构中的最终位置之间的对应关系。我们的目标是了解如何将二维（2D）命运图转换为3D结构。在多个发展系统中回答这个问题很重要，从简单的后生动物到人类。我们的假设是，果蝇期间的3D上皮形态发生是由图案化细胞片内的机械张力的2D分布驱动的。我们将通过对上皮动力学的计算建模和实时成像以及对图案上皮板中的机械张力进行直接分析来检验这一假设。我们的工作将导致经过实验验证的3D上皮形态发生的计算框架。鉴于上皮形态发生的过程的高度保守性质，或研究的结果可能揭示了广泛的发育系统中的上皮动力学。