RETINOIC ACID REGULATED GENES AND EMBRYOS

视黄酸调节基因和胚胎

• 批准号: 6351389
• 负责人: MELISSA B ROGERS
• 金额: $ 33.92万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-07-15 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6351389
• 关键词: beta galactosidase; bone morphogenetic proteins; early embryonic stage; gene induction /repression; laboratory mouse; mammalian embryology; retinoate; teratogens

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.

描述（根据调查员的摘要进行了改编）：类视黄素及其 受体直接调节特定基因的转录，其产物 影响生长，分化或凋亡。或者， 视网膜类似激活的转录因子可以刺激信号的级联 这间接改变了细胞行为。因此，类视黄素直接和间接 启动深刻的发展变化。调查人员表明 视黄酸（RA）和骨形态发生蛋白（BMP）2和4，相互作用 影响胚胎细胞行为。首先，RA直接诱导BMP2基因。 其次，单独暴露于RA或BMP2或BMP4的细胞或RA和RA的组合 BMP的行为不同。差异化，增长率和 诱导凋亡。提出的实验将增加我们的 了解直接涉及的发展和致致造机制 活化的基因，包括BMP2。目的1。确定BMP2是否 视黄酸反应元件（稀有）是正常的BMP2表达所必需的 老鼠。这个目的将检验以下假设：内源性类维生素性信号是 通过比较BMP2序列驱动的B-Galactosidase Reporter基因的发育表达来表达BMP2表达所需的必要 对于那些缺乏罕见的人。 目的2。确定是否畸形水平 类维生素类动物诱导异常BMP2表达。这个目标将检验假设 类维生素类似于视网膜类似的异常BMP2表达是通过检查的表达 ，由RA处理的胚胎中BMP2序列驱动的B-半乳糖苷酶报告基因。 目标3。阐明控制表达的遗传调节元件 F9胚胎癌细胞中BMP2基因的诱导分化为 顶端内胚层由RA并提高营地水平。这个目标将继续我们 控制BMP2的遗传元素的体外解剖 通过识别调节的cAMP响应元件来表达 仅在RA处理的细胞中转录。目标4。直接识别基因 通过将鼠类捕获在酵母中而被RA激活。这个目标将识别基因 直接由RA诱导，因此主要控制信号级联 导致细胞行为的变化。