PBX AND Retinoic Acid-dependent Differentiation

视黄酸（RA）是维生素A的最有效的生物活性形式，在维生素A缺乏症中起着重要作用。 生长、分化、免疫反应、生殖和胚胎发育。母体 维生素A不足和母体维生素A过量与发育异常有关。RA P19胚胎癌细胞的处理导致分化成内胚层或神经元细胞， 这取决于培养条件。前B细胞白血病转录因子1（PBX 1）、PBX 2和PBX 3 mRNA水平和PBX 1/2/3蛋白水平在用RA处理P19细胞后升高。PBX蛋白 在发育过程中作为二聚体伴侣与几种HOX蛋白介导基因表达。这 RA依赖性的PBX 1/2/3表达增加已被证明是分化的关键。 P19细胞向内胚层细胞和神经元细胞的分化。此外，两个基因的表达，骨 形态发生蛋白4（BMP 4）和核心蛋白聚糖（DCN）已被证明需要RA依赖性的增加， PBX 1/2/3在内胚层细胞分化过程中的表达拟议研究的目标是 阐明了在P19细胞分化为 内胚层和神经元细胞。因此，我们计划：（1）进一步表征PBX 172/3蛋白的作用 在P19细胞分化为内胚层细胞、神经细胞和心肌细胞的过程中;（2）确定是否诱导P19细胞的分化， P19细胞RA依赖性分化需要PBX 1/2/3蛋白表达BMP 4和/或DCN 内胚层和/或神经元细胞;和（3）鉴定和表征另外的PBX 1/2/3调节的 P19细胞向内胚层和神经元细胞的RA依赖性分化过程中的基因。这些研究将 进一步了解PBX在哺乳动物发育过程中的作用，并进一步阐明其细节 一种依赖RA的信号通路的信号通路。

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.