PROJECT 1: PMESOGENIN1 IN MESODERMAL DIFFERENTIATIONDIFF OF MOUSE ES CELL

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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.