The role of Sp8 in olfactory system development

Sp8 在嗅觉系统发育中的作用

• 批准号: 7060456
• 负责人: ILYA VILINSKY
• 金额: $ 2.09万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7060456
• 关键词: developmental genetics; developmental neurobiology; gene induction /repression; interneurons; laboratory mouse; mammalian embryology; mutant; neurogenesis; olfactions; olfactory lobe; postdoctoral investigator; respiratory epithelium; telencephalon; transcription factor

DESCRIPTION (provided by applicant): A recently discovered transcription factor, Sp8, is required for limb development and neural tube closure. It is also expressed in specific domains of the medial telencephalon at various points during embryonic development. We believe that this gene could be important in defining the developing olfactory bulbs, as well as the olfactory epithelium. These regions represent some of the few known instances of adult neurogenesis. My project will investigate the role of Sp8 in the telencephalon by using conditional mutant (floxed) Sp8 alleles. These will allow me to recombine out the Sp8 coding sequence, thereby inactivating Sp8 expression, within specific areas at specific times in development. Using a Foxg1-cre allele to drive telencephalic cre expression, I will investigate whether Sp8 is required for olfactory bulb formation, as well as generation of the olfactory epithelium. I will also use a Foxg1-tTA allele as a component of a tetracycline-inducible system to turn on cre expression within the telencephalon. With this technique, I can control the time at which Sp8 is inactivated. This will allow us to investigate later roles of Sp8 during embryonic development, as well as the possible adult requirement for Sp8 in generation of olfactory bulb interneurons.

描述（由申请人提供）：最近发现的转录因子 Sp8 是肢体发育和神经管闭合所必需的。它还在胚胎发育过程中不同点的内侧端脑的特定区域中表达。我们相信该基因对于定义发育中的嗅球以及嗅上皮可能很重要。这些区域代表了一些为数不多的已知成人神经发生实例。我的项目将通过使用条件突变（floxed）Sp8 等位基因来研究 Sp8 在端脑中的作用。这些将使我能够重组 Sp8 编码序列，从而在发育的特定时间的特定区域内使 Sp8 表达失活。使用 Foxg1-cre 等位基因驱动端脑 cre 表达，我将研究 Sp8 是否是嗅球形成以及嗅上皮生成所必需的。我还将使用 Foxg1-tTA 等位基因作为四环素诱导系统的组成部分来开启端脑内的 cre 表达。通过这种技术，我可以控制 Sp8 失活的时间。这将使我们能够研究 Sp8 在胚胎发育过程中的后期作用，以及成年嗅球中间神经元生成过程中对 Sp8 的可能需求。