Centriole Orientation During Left/Right Symmetry in Mice

小鼠左/右对称期间的中心粒方向

• 批准号: 7139654
• 负责人: Wallace Marshall
• 金额: $ 3.84万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7139654
• 关键词: animal tissue; cell morphology; centrosome; cilium; cytoskeleton; embryo /fetus; embryogenesis; fluid flow; fluidity; genetically modified animals; immunofluorescence technique; laboratory mouse; pregnancy; scanning electron microscopy; three dimensional imaging /topography; tomography; vertebrate embryology

DESCRIPTION (provided by applicant): A major unsolved problem in developmental biology is how organisms break symmetry along the left-right body axis. In the mouse, this process involves generation of a leftward fluid flow across the embryonic node. This nodal flow is created, and possibly sensed, by cilia on the node cells. How do the cilia know which way to drive the fluid? Theoretical computations as well as the investigators' preliminary experimental fluid-dynamics studies indicate that cilia could drive a leftward flow if they were tilted to the posterior. Preliminary scanning electron microscopy analysis confirms that such a posterior tilt exists for node cilia. However, how is this tilting aligned relative to the anterior-posterior axis? The direction a cilium points is dictated entirely by the centriole that produces the cilium. The investigators propose to determine the basis of posterior ciliary tilt by examining the orientation of the centrioles which produce the node cilia. They will ask what aspect of centriole orientation is altered in response to anterior-posterior axis cues. As part of this analysis, the investigators will test whether node centrioles are rotationally oriented relative to the midline, as predicted for a mechanosensory model for flow sensing. Taken together, the proposed experiments will test the hypothesis that the centriole is the key structure that links the left-right axis to the anterior-posterior and dorsal-ventral axes. If the investigators find that centrioles are indeed oriented relative to the body axes during left-right determination, this would provide the foundation for future experiments to determine the cell polarity pathways and cytoskeletal elements that produce this defined orientation.

描述（由申请人提供）：发育生物学中一个尚未解决的主要问题是生物体如何沿左右身体轴打破对称。在小鼠中，这一过程涉及到通过胚胎结向左流动的流体的产生。这种节点流是由节点细胞上的纤毛产生并可能被感知的。纤毛是怎么知道液体流向的？理论计算和研究人员的初步实验流体动力学研究表明，如果纤毛向后部倾斜，它们可以驱动向左的气流。初步扫描电镜分析证实这种后倾斜存在于结纤毛。然而，这种倾斜是如何相对于前后轴对齐的呢？纤毛指向的方向完全由产生纤毛的中心粒决定。研究者建议通过检查产生纤毛结的中心粒的方向来确定纤毛后倾的基础。他们会问中心粒方向的哪个方面在响应前后轴信号时发生了改变。作为分析的一部分，研究人员将测试节点中心粒是否相对于中线是旋转定向的，正如流体传感的机械感觉模型所预测的那样。综上所述，拟议的实验将验证一个假设，即中心粒是连接左右轴与前后轴和背腹轴的关键结构。如果研究人员发现中心粒在左右测定过程中确实是相对于体轴定向的，这将为未来的实验提供基础，以确定产生这种定向的细胞极性途径和细胞骨架元件。