Interaction between electrical activity and bone morphogenetic proteins: Consequences to spinal cord differentiation

电活动与骨形态发生蛋白之间的相互作用：脊髓分化的后果

• 批准号: 1120796
• 负责人: Laura Borodinsky
• 金额: $ 92万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1120796&HistoricalAwards=false
• 关键词: Interaction; between; electrical; activity; bone

Connections among neurons and with target cells enable the plethora of nervous system tasks. The establishment of these connections relies on the specialization of neurons during development, which in the spinal cord is regulated by a family of proteins known as bone morphogenetic proteins (BMPs). The current view is that these proteins trigger a genetically hardwired program that establishes the fate of cells along the dorsoventral axis of the developing spinal cord. However, differentiation of embryonic neurons is also sensitive to electrical activity, which manifests spontaneously in these developing cells. This study will test the hypothesis that a gradient of BMPs across the dorsoventral axis of the nervous system contributes to establish a gradient of calcium-dependent electrical activity in immature spinal neurons that, in turn, regulates neuronal differentiation. A multi-approach study using molecular, pharmacological, biochemical and physiological techniques will be implemented. This investigation may lead to new ways of thinking on how the nervous system develops and will challenge the idea that nervous system development is exclusively genetically driven. Results from this project may identify novel mechanisms of action of BMPs of relevance to many research fields, including developmental biology, neuroscience, stem cells and tissue repair. Overall, this study will contribute to the understanding of how to induce restorative plastic events in a pathological context of loss or impaired nervous system function.The PI will serve as role model for female and latino students and colleagues. This award will support both graduate and undergraduate students, and the PI will institute a multistep research experience for the Sacramento High School District in the context of outreach activities coordinated by the Center for Biophotonics. The PI will also continue to support international Neuroscience research in developing countries such as Argentina, through participation in argentine scientific meetings and training courses.

神经元之间以及与靶细胞之间的连接使神经系统能够完成大量任务。这些连接的建立依赖于发育过程中神经元的特化，在脊髓中，神经元的特化受到一种称为骨形态发生蛋白（BMP）的蛋白质家族的调节。目前的观点是，这些蛋白质触发了一个遗传上的硬连线程序，该程序确定了发育中脊髓背腹轴沿着细胞的命运。然而，胚胎神经元的分化也对电活动敏感，这在这些发育中的细胞中自发地表现出来。这项研究将测试的假设，即梯度的BMP跨背腹轴的神经系统有助于建立一个梯度的钙依赖性的电活动在未成熟的脊髓神经元，反过来，调节神经元的分化。将采用分子、药理学、生物化学和生理学技术进行多方法研究。这项研究可能会导致对神经系统如何发育的新思维方式，并将挑战神经系统发育完全由基因驱动的观点。该项目的结果可能会确定与许多研究领域相关的BMP的新作用机制，包括发育生物学，神经科学，干细胞和组织修复。总的来说，这项研究将有助于了解如何在神经系统功能丧失或受损的病理背景下诱导恢复性整形事件。PI将成为女性和拉丁美洲学生和同事的榜样。该奖项将支持研究生和本科生，PI将在生物光子学中心协调的外展活动背景下为萨克拉门托高中区提供多步研究经验。PI还将通过参加阿根廷科学会议和培训课程，继续支持阿根廷等发展中国家的国际神经科学研究。