PBX AND Retinoic Acid-dependent Differentiation

PBX 和视黄酸依赖性分化

基本信息

批准号：
8006977
负责人：
DIANNE R SOPRANO
金额：
$ 9.98万
依托单位：
TEMPLE UNIV OF THE COMMONWEALTH
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-01-15 至 2010-12-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Retinoic acid (RA), the most potent biologically active form of vitamin A, plays an important role during growth, differentiation, immune response, reproduction, and embryonic development. Both maternal insuffiency and maternal excess of vitamin A are associated with developmental abnormalities. RA treatment of P19 embryonal carcinoma cells causes differentiation to either endodermal or neuronal cells, depending on the culture conditions. Pre-B cell leukemia transcription factor 1 (PBX1), PBX2 and PBX3 mRNA levels, and PBX1/2/3 protein levels are elevated upon treatment of P19 cells with RA. PBX proteins function as dimeric partners with several HOX proteins mediating gene expression during development. This RA-dependent increase in PBX1/2/3 expression has been demonstrated to be critical for differentiation of P19 cells to both endodermal and neuronal cells. In addition, the expression of two genes, bone morphogenetic protein 4 (BMP4) and decornin (DCN) have been shown to require RA-dependent increase in PBX1/2/3 expression during endodermal cell differentiation. The goal of the proposed studies is to elucidation the role of this RA-dependent increase in PBX1/2/3 levels during differentiation of P19 cells to endodermal and neuronal cells. We therefore plan: (1) to further characterize the role of PBX172/3 proteins during differentiation of P19 cells to endodermal, neuronal and cardiac cells; (2) to determine if induction of BMP4 and/or DCN expression by PBX1/2/3 proteins is required for RA-dependent differentiation of P19 cells to endodermal and/or neuronal cells; and (3) to identify and characterize additional PBX1/2/3-regulated genes during RA-dependent differentiation of P19 cells to endodermal and neuronal cells. These studies will further the understanding of the role of PBX during mammalian development and further elucidate the details of one RA-dependent pathway of signaling during differentiation.

描述（由申请人提供）：视黄酸（RA）是维生素A的最有效的生物活性形式，在生长，分化，免疫反应，繁殖和胚胎发育中起重要作用。孕产妇的不足和孕妇过量维生素A都与发育异常有关。 p19胚胎癌细胞的RA处理会导致内皮细胞或神经元细胞分化，具体取决于培养条件。 PRE-B细胞白血病转录因子1（PBX1），PBX2和PBX3 mRNA水平以及PBX1/2/3蛋白水平在用RA处理P19细胞后升高。 PBX蛋白在发育过程中介导基因表达的几种HOX蛋白充当二聚体伙伴。 PBX1/2/3表达中RA依赖性的增加已被证明对于将p19细胞分化为内胚层和神经元细胞至关重要。另外，两种基因的表达，即骨形态发生蛋白4（BMP4）和解糖蛋白（DCN）的表达，已证明需要在内胚层细胞分化过程中PBX1/2/3表达的RA依赖性增加。拟议的研究的目的是阐明P19细胞与内胚层和神经元细胞分化期间PBX1/2/3水平的这种RA依赖性增加的作用。因此，我们计划：（1）进一步表征PBX172/3蛋白在p19细胞分化为内胚层，神经元和心脏细胞中的作用；（2）确定PBX1/2/3蛋白是否诱导BMP4和/或DCN表达是否需要RA依赖性p19细胞与内胚层和/或神经元细胞的RA依赖性分化；（3）在p19细胞与内胚层和神经元细胞的RA依赖性分化过程中，识别和表征其他PBX1/2/3调节的基因。这些研究将进一步了解PBX在哺乳动物发育中的作用，并进一步阐明在分化过程中一种RA依赖性途径的细节。