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(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。在胚胎发育的不同时间点，它也在内侧端脑的特定区域表达。我们认为，这个基因在定义发育中的嗅球和嗅觉上皮细胞方面可能很重要。这些区域代表了为数不多的成人神经发生的已知实例。我的项目将通过使用条件突变的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出SP8编码序列，从而在发育的特定时间在特定区域内灭活SP8的表达。使用FOXG1-cre等位基因来驱动端脑cre的表达，我将研究SP8是否对嗅球的形成以及嗅觉上皮的生成是必需的。我还将使用FOXG1-TTA等位基因作为四环素诱导系统的一个组成部分，以开启端脑中cre的表达。使用这项技术，我可以控制SP8被停用的时间。这将使我们能够研究SP8在胚胎发育过程中的后续作用，以及成年后对SP8在嗅球中间神经元生成中的可能需求。