PROJECT 1: PMESOGENIN1 IN MESODERMAL DIFFERENTIATIONDIFF OF MOUSE ES CELL

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。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、细胞和遗传调控。我们的重点是bHLH转录因子pMesogenin1，这是正常的近轴中胚层发育所必需的。为了了解pMesogenin1的作用机制，我们对pMesogenin1无基因型和野生型胚胎进行了转录组分析。在pMesogenin1-样品中表达增加的一个基因编码一种新的分泌蛋白，Cristin1（富含半胱氨酸和单TSR结构域的蛋白1）。在检索序列数据库中，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种新蛋白家族的生物活性上。分子、生化和细胞生物学数据表明，cristin通过Frizzled/LRP6调节β -连环蛋白信号传导，从而模仿Wnt配体信号传导活性（JBC, press 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中的发育作用。

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). 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.