Role of Par Genes in the Early Mouse Embryo

Par 基因在早期小鼠胚胎中的作用

• 批准号: 6960596
• 负责人: VERNADETH B ALARCON
• 金额: $ 6.82万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-06 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6960596
• 关键词: RNA interference; cell type; cellular polarity; developmental genetics; early embryonic stage; fluorescence microscopy; fluorescent dye /probe; gene expression; genetic regulation; immunocytochemistry; laboratory mouse; molecular biology; polymerase chain reaction

DESCRIPTION (provided by applicant): The generation of cell polarity is a fundamental process that controls cell behavior during animal embryogenesis. In lower vertebrates, egg polarity plays an essential role in patterning the embryonic body. In mammals such as the mouse, however, the cellular polarization at the 8-cell stage is responsible for the formation of 2 different cell populations in the blastocyst: trophectoderm (TE) and inner cell mass (ICM). The outer, polarized cells give rise to TE, the founder of the placenta, while the inner, non-polarized cells become ICM, the founder of fetal tissues. Thus, the misregulation of cell polarization in the mammalian embryo could disrupt the cell lineages of the blastocyst, resulting in reproductive failure or disease due to aberrant development into embryo-derived cancer. The long-term goal of the proposed research is to elucidate the molecular mechanisms that initiate cell polarization in mouse early development, which is currently not well understood. A conserved molecular mechanism regulates cell polarity in various animal cells. This mechanism involves the partitioning defective (Par) genes, which were originally isolated in the nematode. Based on database searches of gene sequences, the investigator identified 18 Par homologs in the mouse genome. Our preliminary studies revealed that transcripts of many of the Par genes are expressed from the ovary to the blastocyst stage. The proposed project is a pilot study that will pursue one specific aim, which is to determine whether the Par genes are necessary for normal early development. The investigator will examine which of the 18 mouse Par genes are indispensable in early development, specifically with regards to cell polarization and TE/ICM development during blastocyst formation. She will employ the RNAi approach to down-regulate Par gene expression during early development. Thus, the project will clarify the importance of Par genes in establishing cell polarity and the first 2-cell lineages in the mouse embryo. An understanding of cell polarization in the mouse embryo should have significant benefit for human health research related to reproductive problems.

描述（由申请人提供）：细胞极性的产生是动物胚胎发生过程中控制细胞行为的基本过程。在低等脊椎动物中，卵的极性在胚胎体的形成中起着重要的作用。然而，在哺乳动物如小鼠中，在8-细胞阶段的细胞极化负责在胚泡中形成2种不同的细胞群：滋养外胚层（TE）和内细胞团（ICM）。外层的极化细胞产生TE，这是胎盘的创始者，而内层的非极化细胞成为ICM，这是胎儿组织的创始者。因此，哺乳动物胚胎中细胞极化的失调可能破坏胚泡的细胞谱系，导致生殖失败或由于异常发育成胚胎衍生的癌症而引起的疾病。这项研究的长期目标是阐明在小鼠早期发育中启动细胞极化的分子机制，目前还不清楚。在各种动物细胞中，一种保守的分子机制调节细胞极性。这种机制涉及分配缺陷（Par）基因，这是最初在线虫中分离。基于基因序列的数据库搜索，研究人员在小鼠基因组中鉴定了18个Par同源物。我们的初步研究表明，许多Par基因的转录本表达从卵巢到囊胚阶段。拟议的项目是一项试点研究，将追求一个特定的目标，即确定Par基因是否是正常早期发育所必需的。研究人员将检查18个小鼠Par基因中哪些基因在早期发育中是必不可少的，特别是在囊胚形成期间的细胞极化和TE/ICM发育方面。她将采用RNAi方法在早期发育过程中下调Par基因表达。因此，该项目将阐明Par基因在小鼠胚胎中建立细胞极性和第一个2细胞谱系中的重要性。对小鼠胚胎细胞极化的理解对与生殖问题相关的人类健康研究有重大意义。