Eph Signaling Auditory Brainstem Development

Eph 信号听觉脑干发育

• 批准号: 7068007
• 负责人: Karina S Cramer
• 金额: $ 25.67万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7068007
• 关键词: auditory nuclei; axon; biological signal transduction; brain stem; chick embryo; cochlea; cochlear nerve; developmental neurobiology; electroporation; ephrins; growth factor; immunocytochemistry; laboratory mouse; ligands; neurogenesis; neuronal guidance; plasmids; protein tyrosine kinase; receptor expression; species difference; synapses

DESCRIPTION (provided by applicant): The proposed research addresses potential molecular mechanisms underlying the formation of precise synaptic connections in the auditory brainstem. The applicant has previously shown that several members of the Eph family of receptor tyrosine kinases are expressed in avian auditory brainstem nuclei and along the midline during the formation of synaptic connections. These receptors mediate cell-cell interactions during axon outgrowth, and gradients of Eph receptors and their ligands, the ephrins, are required for the formation of precise topographic maps in the visual system. The Specific Aims are to test the roles of Eph receptor signaling in the development of auditory brainstem projections. Each group of experiments includes both descriptive studies of developmental expression and functional studies using experimental manipulations. Inovo microelectroporation will be used to misexpress Eph receptors and an in vitro labeling method will be used to evaluate resulting axonal projections. The generality of findings from chicks will be examined in developing mouse brainstem. Specific Aim 1 proposes experiments to investigate whether gradients of Eph receptors and ephrins are essential for the development of the tonotopic projection from VllIth nerve axons to the avian cochlear nucleus, n. magnocellularis. Specific Aim 2 extends these studies to mammals. The Eph receptor EphA4 is expressed nonuniformly in the developing mouse cochlear nuclei. The role of EphA4 in the establishment of a homologous projection from the VIIIth nerve to the cochlear nucleus will be evaluated in mutant mice that lack EphA4. Axonal projections from n. magnocellularis branch so that an ipsilateral branch synapses in the dorsal region of the target, n. laminaris, while the contralateral branch grows across the dorsal midline and contacts the ventral region of contralateral n. laminaris. Experiments outlined in Specific Aim 3 will evaluate the role of Eph receptors in the guidance of cochlear nucleus axons at the midline in the avian brainstem. These experiments will test whether Eph signaling is extensively used in the development of pathways in the auditory brainstem, and will address whether the roles for Eph receptors in establishing synaptic specificity are similar across modalities and across species.

描述（由申请人提供）： 提出的研究探讨了听觉脑干中精确突触连接形成的潜在分子机制。申请人先前已经表明，EPH受体酪氨酸激酶的几个成员在突触连接形成期间在鸟类听觉脑干核和中线中表达。这些受体介导轴突出生过程中的细胞细胞相互作用，EPH受体及其配体的梯度是在视觉系统中形成精确的地形图所必需的。具体目的是测试EPH受体信号在听觉脑干投影发展中的作用。每组实验既包括使用实验操作的发育表达和功能研究的描述性研究。 INOVO微电器将用于Misexpress EPH受体，并将使用一种体外标记方法来评估产生的轴突投影。在发展小鼠脑干时，将检查来自小鸡的发现的普遍性。具体目的1提出了实验，以研究EPH受体和埃弗林的梯度是否对于从Vllith神经轴突到鸟根耳蜗核的构成型投影的发展是否至关重要。大细胞。具体目标2将这些研究扩展到哺乳动物。 EPH受体EPHA4在发育中的小鼠耳蜗核中不均匀表达。 Epha4在缺乏Epha4的突变小鼠中评估Epha4在建立从Viiith神经到耳蜗核的同源投影中的作用。 n。大细胞分支，因此在目标的背侧区域的同侧分支突触n。地层，而对侧分支在背侧中线生长，并接触对侧n的腹侧区域。拉米纳利人。特定目标3中概述的实验将评估EPH受体在鸟类脑干中线的耳蜗核心轴突指导中的作用。这些实验将测试EPH信号是否广泛用于听觉脑干中的途径，并将解决EPH受体在建立突触特异性中的作用是否相似。