Molecular mechanisms regulating mitral cell development

调节二尖瓣细胞发育的分子机制

• 批准号: 8793240
• 负责人: Fumiaki Imamura
• 金额: $ 8.41万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8793240
• 关键词: Molecular; mechanisms; regulating; mitral; cell

ABSTRACT The olfactory bulb (OB) is the first relay station of olfactory information in the central nervous system (CNS). The general laminar organization and elaborate morphologies of OB projection neurons, mitral/tufted cells, have been well known for several decades, but we continue to lack insight into their developmental mechanisms. Previous studies revealed the timeline of anatomical changes of developing mitral cells. The next step is to understand the molecular determinants and pathways regulating the specific anatomical changes occurring during mitral/tufted cell development, which is the long-term goal of this project. To accomplish this goal, I have established a novel method to manipulate molecular expression in subsets of developing mitral cells. Using this method, this proposal seeks to investigate the roles of several candidate molecules in mitral cell development. The candidate molecules are three transcription factors (Tbr1, Tbr2, Tbx21), an extracellular matrix molecule (Reelin), a transmembrane protein (Protocadherin21), and a synaptic vesicle protein (vGluT1). All of these candidate molecules have been selected because they are specifically expressed by mitral/tufted cells in developing OB. In Aim 1, the temporal expression pattern of candidate molecules in developing mitral cells will be established. In Aim 2, the fate of mitral cell precursors in the absence of Tbr1 or Tbr2 will be determined. In Aim 3, I will test hypotheses regarding the roles of Tbx21, Reelin, Protocadherin21, and vGluT1 in morphological development and/or synapse formation of mitral cells. These studies will provide us with new significant insights into molecular determinants and pathways working in developing mitral cells, which can then serve as a stepping stone to further research. I believe that this will become one of the leading works for neuronal circuitry formation during development of both the OB and elsewhere in the CNS where these molecules are expressed.

抽象的 嗅球（OB）是中枢神经系统（CNS）中嗅觉信息的第一个中继站。 OB 投射神经元、二尖瓣/簇状细胞的一般层状组织和精细形态， 几十年来，它们已广为人知，但我们仍然缺乏对其发展的深入了解 机制。先前的研究揭示了发育中的二尖瓣细胞的解剖变化的时间表。 下一步是了解调节特定解剖学的分子决定因素和途径 二尖瓣/簇状细胞发育过程中发生的变化是该项目的长期目标。到 为了实现这个目标，我建立了一种新方法来操纵子集中的分子表达 发育中的二尖瓣细胞。该提案旨在使用这种方法来调查几位候选人的角色 二尖瓣细胞发育中的分子。候选分子是三个转录因子（Tbr1、Tbr2、 Tbx21)、细胞外基质分子 (Reelin)、跨膜蛋白 (Protocadherin21) 和 突触小泡蛋白（vGluT1）。所有这些候选分子都被选中，因为它们是 由发育中的 OB 中的二尖瓣/簇状细胞特异性表达。在目标 1 中，时间表达模式 将建立发育二尖瓣细胞的候选分子。在目标 2 中，二尖瓣细胞的命运 将测定不存在 Tbr1 或 Tbr2 时的前体。在目标 3 中，我将测试有关以下方面的假设： Tbx21、Reelin、Protocadherin21 和 vGluT1 在形态发育和/或突触中的作用 二尖瓣细胞的形成。这些研究将为我们提供关于分子生物学的新的重要见解。 决定因素和途径在二尖瓣细胞的发育中起作用，然后可以作为踏脚石 进一步研究。我相信这将成为神经回路形成的领先著作之一 在 OB 和 CNS 中表达这些分子的其他地方的发育过程中。