LUNATIC FRINGE, SOMITOGENESIS AND SEGMENTATION CLOCKS

疯狂边缘、体细胞发生和分段时钟

• 批准号: 6013464
• 负责人: SUSAN E COLE
• 金额: $ 3.17万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6013464
• 关键词: artificial chromosomes; gene expression; genetic mapping; genetic regulatory element; genetically modified animals; laboratory mouse; mammalian embryology

During development, the establishment of boundaries within fields of cells can direct their future growth and patterning. Fringe has been shown to play an important role in the establishment of these boundaries during Drosophila development. Mammalian homologs of fringe have been identified and evidence suggests that they play a similar role in vertebrate patterning. Specifically, Lunatic fringe (Lfng) has been shown to be involved in establishing developmental boundaries during somitogenesis, and has further been demonstrated to be linked to a newly described segmentation clock that regulates somitogenesis. Mouse transgenesis will be used to functionally identify cis-acting regulatory elements that control the precise tissue and developmentally restricted expression of Lfng, and that tie its expression pattern to a segmentation clock. Localization of these regions will facilitate the identification of these regulatory elements on a DNA level. These regulatory regions will also play a critical role in studies of functional overlap within the fringe gene family by permitting controlled ectopic expression of other family members in the expression pattern of Lfng. Fringe proteins play a key role in the modulation of the Notch signaling pathway, thus these studies will be directly relevant to determining the role and regulation of this pathway in normal development. This pathway has been implicated in several human diseases including cancer, Alagille syndrome and CADASIL syndrome, and the further studies of these health problems will be enhanced by increased knowledge of the underlying biology.

在开发过程中，在细胞领域内建立边界可以指导其未来的增长和模式。 在果蝇开发过程中，边缘在建立这些边界方面起着重要作用。 已经确定了边缘的哺乳动物同源物，证据表明它们在脊椎动物图案中起着相似的作用。具体而言，已证明疯子条纹（LFNG）参与了在体内发生过程中建立发育边界，并进一步证明与调节体型发生的新描述的分割时钟相关。 小鼠转基因将用于识别控制精确组织和发育限制LFNG表达的顺式作用调节元件，并将其表达模式与分割时钟联系起来。 这些区域的定位将有助于在DNA水平上识别这些调节元素。 这些调节区域还将通过允许在LFNG的表达模式中允许其他家族成员的异位表达在边缘基因家族内的功能重叠研究中起关键作用。 条纹蛋白在调节Notch信号通路中起关键作用，因此这些研究将与确定该途径在正常发育中的作用和调节直接相关。 该途径与包括癌症，阿拉吉尔综合征和卡达西尔综合征在内的几种人类疾病有关，对这些健康问题的进一步研究将通过对潜在生物学的知识增加来增强。