Tensile stress in orienting planar cell polarity

定向平面细胞极性的拉应力

• 批准号: 8331372
• 负责人: Christopher Robert Kintner
• 金额: $ 22.1万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8331372
• 关键词: Affect; Anterior; Apical; Biocompatible Materials; Biological Assay; Biological Models; Brain; Cell Differentiation process; Cell Polarity; Cells; Cerebral Ventricles; Cilia; Cues; Defect; Development; Developmental Process; Devices; Diagnosis; Distal; Ectoderm; Embryo; Embryonic Development; Epithelium; Event; Fibronectins; Glass; Goals; Health; Homologous Gene; Human; Individual; Lung; Maps; Measures; Mediating; Mesoderm; Modeling; Morphology; Mucous body substance; Nature; Organ; Pathway interactions; Pattern; Play; Primary Ciliary Dyskinesias; Process; Research; Role; Signal Pathway; Signal Transduction; Skin; Specific qualifier value; Staging; Stress; Study models; Sum; Surface; Syndrome; Testing; Time; Tissues; To specify; Work; base; body system; fluid flow; gastrulation; human disease; novel; prospective; reproductive; research study; respiratory

DESCRIPTION (provided by applicant): In many organ systems, cells projecting hundreds of beating cilia, called multiciliate cells, produce a vigorous fluid flow that transports biological materials along luminal surfaces. Multiciliate cells populate the respiratory and reproductive tracts, and the ventricles of the brain, and the flow they produce has significant implications for human health. To be effective in organ function, ciliary flow has to direct along a specific axis: in the lung, for example, flow propels mucus out of rather than deeper into the airways. To produce directed flow, developing epithelia need to acquire a planar axis, thus orienting cilia beating within a cell, as well as between cells. To determine how multiciliate cells acquire planar cell polarity (PCP), we have pioneered a model system, namely the X. laevis larval skin. Multiciliate cells begin to differentiate in the developing skin soon after gastrulation, producing a vigorous ciliary flow that invariably is directed from anterior to posterior. A global patterning event that occurs during gastrulation is known to fix the direction of ciliary flow, but nothing is known about the mechanisms that mediate this patterning event as is the case in all other known examples of PCP. In this exploratory proposal, we will test a new model where the direction of planar polarity is dictated in part by the orientation of tensile stress that occurs in the tissue during embryogenesis. In the case of the skin, this tensile stress occurs during gastrulation via the forces generated by mesoderm during involution and axial elongation. Specifically, we will employ a device, called the tractor pull, to apply oriented stress to isolated developing skin, at stages when the planar axis is normally established. These experiments will extend on preliminary findings, determine the parameters by which oriented stress can specify a planar axis, and determine whether oriented stress works upstream or in parallel with the PCP signaling pathway. In sum, the experiments proposed here will provide an important proof of principle, thus establishing a new model for studying how forces in the embryo sculpt and pattern tissues.

描述（由申请人提供）：在许多器官系统中，投射数百个纤毛的细胞，称为多重细胞，产生急剧的流体流动，可沿着腔表面运输生物材料。多核细胞填充呼吸道和生殖道，大脑的心室以及它们产生的流量对人类健康具有重要意义。要在器官功能上有效，睫状流必须沿特定的轴指导：例如，在肺中，流动促进粘液从呼吸道中而不是深入到气道中。为了产生有向流的流动，发展上皮需要获取平面轴，从而使纤毛在细胞内以及细胞之间取代。为了确定多性细胞如何获得平面细胞极性（PCP），我们已经开创了模型系统，即X. laevis幼虫皮。胃结构后不久，多核细胞开始在发育中的皮肤中分化，产生剧烈的睫状流，总是从前到后的。众所周知，在胃肠道过程中发生的全球模式事件可以固定睫状流的方向，但是在所有其他已知的PCP示例中，对介导这种图案事件的机制尚无知之甚少。在此探索性建议中，我们将测试一个新模型，在该模型中，平面极性的方向部分取决于胚胎发生过程中组织中发生的拉伸应力的方向。在皮肤的情况下，这种拉伸应力发生在胃肠道期间，通过中胚层产生的力和轴向伸长期间产生的力。具体而言，我们将使用一种称为拖拉机拉力的设备，在通常建立平面轴时，在阶段将定向的压力应用于孤立的发育型皮肤。这些实验将扩展到初步发现，确定定向应力可以指定平面轴的参数，并确定定向应力是否在上游或与PCP信号通路并行相关。总而言之，此处提出的实验将提供一个重要的原理证明，从而建立了一个新模型，用于研究胚胎雕塑和图案组织中的力。