PROJECT 1: PMESOGENIN1 IN MESODERMAL DIFFERENTIATIONDIFF OF MOUSE ES CELL

项目 1：小鼠 ES 细胞中胚层分化中的 Pmesogenin1

• 批准号: 7382092
• 负责人: JEONG YOON
• 金额: $ 24.81万
• 依托单位: MAINEHEALTH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7382092
• 关键词: PROJECT; PMESOGENIN1; MESODERMAL; DIFFERENTIATIONDIFF; MOUSE

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our research focuses on the molecular, cellular, and genetic regulation of mesoderm differentiation in embryonic stem (ES) cells, and during development. Our focus is on the bHLH transcription factor, pMesogenin1, which is required for proper paraxial mesoderm development. Towards understanding pMesogenin1's action mechanisms, we performed transcriptome analyses in pMesogenin1 null and wild type embryos. One gene whose expression was increased in pMesogenin1- samples encodes a novel secreted protein, Cristin1 (cysteine-rich and single TSR domain containing protein 1). In searching sequence databases, we identified three Cristin1 homologues in the mouse genome (Cristin 2, 3, and 4). Recent efforts focus primarily on determining the biological activities of this novel protein family. Molecular, biochemical, and cell biological data indicate that Cristins modulate beta-catenin signaling through Frizzled/LRP6, thereby mimicking Wnt ligand signaling activity (JBC in press 2006). We now are purifying biologically active recombinant Cristin proteins, and determining their developmental roles especially during mesodermal cell growth and differentiation.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。我们的研究重点是胚胎干（ES）细胞和发育过程中中胚层分化的分子、细胞和遗传调节。我们的重点是bHLH转录因子，pMesogenin 1，这是所需的适当近轴中胚层的发展。为了了解pMesogenin 1的作用机制，我们在pMesogenin 1 null和野生型胚胎中进行了转录组分析。在pMesogenin 1-样品中表达增加的一个基因编码一种新的分泌蛋白，Cristin 1（富含半胱氨酸且含有单一TSR结构域的蛋白1）。在搜索序列数据库中，我们确定了三个Cristin 1同源物在小鼠基因组（Cristin 2，3和4）。最近的努力主要集中在确定这个新的蛋白质家族的生物活性。分子、生物化学和细胞生物学数据表明，Cristins通过Frizzled/LRP 6调节β-连环蛋白信号传导，从而模拟Wnt配体信号传导活性（JBC，出版2006）。我们现在正在纯化具有生物活性的重组Cristin蛋白，并确定它们在中胚层细胞生长和分化过程中的发育作用。