RETINOIC ACID REGULATED GENES AND EMBRYOS

描述(改编自研究人员摘要)：维甲酸及其 受体直接调节特定基因的转录，其产物 影响生长、分化或细胞凋亡。或者， 维甲酸激活的转录因子可以刺激信号的级联 间接改变了细胞的行为。因此，维甲酸直接或间接地 引发深刻的发展变革。调查人员已经证明 维甲酸(RA)和骨形态发生蛋白(BMPs)2和4相互作用 影响胚胎细胞的行为。首先，RA直接诱导BMP2基因。 第二，细胞暴露于RA或BMP2或BMP4，或RA和BMP4的组合 BMP的行为有所不同。分化、生长速度和 诱导细胞凋亡的发生。拟议的实验将增强我们的 对发育和致畸机制的认识 激活的基因，包括BMP2。目的1.确定BMP2是否 维甲酸反应元件(REARE)是BMP2正常表达所必需的 老鼠。这个目标将检验这样的假设，即内源性视黄醇信号是 通过比较含有稀有基因的BMP2序列驱动的B-半乳糖苷酶报告基因的发育表达，得出BMP2表达所必需的 对于那些缺乏稀有的人。目的2.确定致畸水平 类维甲酸可诱导BMP2异常表达。这一目标将检验这一假设 这种异常的BMP2表达是由维甲酸诱导的，通过检测 在RA处理的胚胎中，BMP2序列驱动的B-半乳糖苷酶报告基因。 目的3.阐明控制该基因表达的基因调控元件 BMP2基因在F9胚胎癌细胞诱导分化为 RA引起的顶叶内胚层和cAMP水平升高。这一目标将继续我们的 控制BMP2的遗传因素的系统体外剖析 通过识别调节cAMP反应元件来表达 仅在RA处理的细胞中转录。目的4.直接识别基因 由RA激活，通过在酵母中捕获小鼠稀有动物而激活。这一目标将识别基因 直接由RA诱导，因此在控制信号级联中起主要作用 导致细胞行为的改变。

DESCRIPTION (adapted from investigator's abstract): Retinoids and their receptors directly modulate the transcription of specific genes, whose products influence growth, differentiation, or apoptosis. Alternatively, retinoid-activated transcription factors can stimulate cascades of signaling that indirectly alter a cell behavior. Thus, retinoids directly and indirectly initiate profound developmental changes. The investigators have shown that retinoic acid (RA) and bone morphogenetic proteins (BMPs) 2 and 4, interact to influence embryonic cell behavior. First, RA directly induces the Bmp2 gene. Second, cells exposed to RA or BMP2 or BMP4 alone or the combination of RA and a BMP behave differently. Changes in differentiation, growth rate, and the induction of apoptosis occur. The proposed experiments will augment our understanding of developmental and teratogenic mechanisms involving directly activated genes, including Bmp2. Aim 1. To determine whether or not the Bmp2 retinoic acid response element (RARE) is required for normal Bmp2 expression in mice. This aim will test the hypothesis that an endogenous retinoid signal is necessary for Bmp2 expression by comparing the developmental expression of B-galactosidase reporter genes driven by Bmp2 sequences containing the RARE to those lacking the RARE. Aim 2. To determine whether or not teratogenic levels of retinoids induce aberrant Bmp2 expression. This aim will test the hypothesis that aberrant Bmp2 expression is induced by retinoids by examining the expression of ,B-galactosidase reporter genes driven by Bmp2 sequences in RA-treated embryos. Aim 3. To elucidate the genetic regulatory elements controlling the expression of the Bmp2 gene in F9 embryonal carcinoma cells induced to differentiate into parietal endoderm by RA and increased cAMP levels. This aim will continue our systematic in vitro dissection of the genetic elements controlling Bmp2 expression by identifying the cAMP response element that modulates transcription only in RA-treated cells. Aim 4. To identify genes directly activated by RA by trapping murine RAREs in yeast. This aim will identify genes directly induced by RA and thus primary in controlling signaling cascades leading to changes in cell behavior.