PROJECT 1: PMESOGENIN1 IN MESODERMAL DIFFERENTIATIONDIFF OF MOUSE ES CELL

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们的研究集中在胚胎干细胞中中胚层分化的分子、细胞和遗传调控以及发育过程中。我们的重点是bHLH转录因子pMesgenin1，它是正常的旁轴中胚层发育所必需的。为了了解pMesgenin1‘S的作用机制，我们对pMesgenin1缺失和野生型胚胎进行了转录组分析。在pMesgenin1-样本中表达增加的一个基因编码一种新的分泌蛋白Cristin1(富含半胱氨酸的单一TSR结构域包含蛋白1，也称为R-Spin3)。在搜索序列数据库中，我们在小鼠基因组中发现了三个Cristin1同源物(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学活性上。分子、生化和细胞生物学数据表明，Cristins通过FrizzledLRP6调节β-连环蛋白信号，从而模拟Wnt配体的信号活动(JBC 2006)。我们现在的重点是确定Cristins在发育中的生物学作用。

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, also known as R-spondin3). 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 2006). We now are focusing on determining the biological role of Cristins in development.