Mechanosensitive Regulation of Axon Guidance

任何模型实验系统的有用性取决于它能够模拟正常体内反应的程度。 一个恰当的例子是使用受控组织培养环境来研究神经元如何生长的模型。大多数研究人员未能解释神经元在胚胎中遇到的所有关键影响，特别是胚胎组织的机械行为。这一遗漏被证明是至关重要的。私家侦探的证据。的实验室表明，除非组织培养环境模仿胚胎的机械状态，否则某些神经元无法对关键的指导线索做出正常反应。关于机械信号如何影响神经元对分子引导线索的反应，我们知之甚少。这些实验使用P.I.开发的组织培养模型解决了这一缺陷。来解释胚胎的机械状态。他们专注于一种蛋白质，这种蛋白质在神经元如何对机械和分子信号做出反应方面起着关键的调节作用。为了解开协调胚胎中神经元对分子指导线索的反应的机制，这些研究人员将使用生物化学和分子方法来操纵机械环境。他们的最终目标是构建一个与神经元和其他机械敏感细胞具有最大体内相关性的组织培养模型。这项工作具有更广泛的影响，凭借两个K-12外展计划建立的PI。第一个项目赞助了200多名内城学生在研究实验室进行基于调查的项目。第二个国家为教师确立了专业发展。该奖项将扩大学生和教师参与真实探究式研究的机会，加强STEM教育渠道。

The usefulness of any model experimental system depends on the extent to which it is able to mimic normal in vivo responses. A case in point is models that use controlled tissue culture environments to investigate how neurons grow. Most researchers fail to account for all key influences that neurons encounter in the embryo, particularly the mechanical behavior of embryonic tissue. This omission turns out to be critical. Evidence from the P.I.'s laboratory shows that unless the tissue culture environment mimics the mechanical status of the embryo, certain neurons are unable to respond normally to critical guidance cues. Very little is known about how mechanical signals impact neuronal responses to molecular guidance cues. These experiments address that deficit using a tissue culture model developed by the P.I. to account for the mechanical status of the embryo. They focus on a protein that plays a key regulatory role in how neurons respond to both mechanical and molecular signals. With the aim of unraveling mechanisms that coordinate neuronal responses to molecular guidance cues in the embryo, these investigators will use biochemical and molecular approaches to manipulate the mechanical environment. Their ultimate goal is to construct a tissue culture model with maximum in vivo relevance to both neurons and other mechanosensitive cells. The work has broader impact by virtue of two K-12 outreach programs established by the P.I. The first has sponsored over 200 inner city students to perform inquiry-based projects in research laboratories. The second has established professional development for their teachers. This award will expand opportunities for both students and their teachers to participate in authentic inquiry-based research, reinforcing the STEM educational pipeline.