Dorsal-Ventral Pattern Formation in the Zebrafish Embryo

斑马鱼胚胎背腹模式的形成

• 批准号: 6913704
• 负责人: Mary C. Mullins
• 金额: $ 34.87万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6913704
• 关键词: biological signal transduction; bone morphogenetic proteins; developmental genetics; gene mutation; genetically modified animals; vertebrate embryology; zebrafish

DESCRIPTION (provided by applicant): Pattern formation along the dorsal-ventral (DV) embryonic axis is fundamental in the establishment of the diverse cell types found in vertebrate embryos. A Bone Morphogenetic Protein (BMP) signaling pathway is key in this pattern formation process. BMPs are postulated to act as morphogens to establish distinct cell fates along the DV axis. Current models for dorsal-ventral patterning and the BMP signaling gradient are still rather basic in nature, however, due to difficulties in addressing key questions regarding BMP gradient action. A number of new molecular genetic tools, combined with unique cellular methods in the zebrafish, will be exploited in this proposal to significantly extend upon the current models of vertebrate DV patterning. Two issues central to models of DV patterning and BMP signaling will be investigated. First the temporal action of the BMP gradient in DV patterning will be tested using inducible transgenes. It will be determined if the gradient acts coordinately during gastrulation to specify all ventrolateral cell fates or if it acts at multiple time points. Secondly, spatial aspects of the BMP signaling gradient will be examined. An effective gastrula BMP signaling gradient range will be defined under normal physiological conditions, which actively specifies distinct cell types during a given time period in vivo, key properties of morphogens. The spatial extent of the gradient will be examined functionally. Lastly, to maximize understanding of DV patterning and BMP gradient generation, regulation, and action through loss-of-function studies, it is critical to identify all the genetic players in the pathway. To this end, an uncharacterized dorsalized mutant gene will be analyzed, which may be a novel component of this pathway. These studies are directly relevant to the study of human disease, since some of the genes in this pathway have been shown or are implicated in the cause of multiple human disease states and human inherited disorders.

描述（由申请人提供）：在脊椎动物胚胎中发现的不同细胞类型的建立中，沿着背腹（DV）胚胎轴的模式形成是基本的。骨形态发生蛋白（BMP）信号通路是这种模式形成过程的关键。骨形成蛋白被假定作为形态发生素，沿DV轴沿着建立不同的细胞命运。然而，由于难以解决有关BMP梯度作用的关键问题，目前的背腹图案和BMP信号梯度模型在本质上仍然是相当基本的。一些新的分子遗传学工具，结合独特的细胞方法在斑马鱼，将利用在这个建议显着扩展后，目前的脊椎动物DV模式。DV模式和BMP信号传导模型的两个核心问题将被研究。首先，将使用诱导型转基因测试DV图案化中BMP梯度的时间作用。将确定梯度是否在原肠胚形成期间协调作用以指定所有腹外侧细胞结局或是否在多个时间点作用。其次，将检查BMP信号梯度的空间方面。将在正常生理条件下定义有效的原肠胚BMP信号传导梯度范围，其在体内给定时间段内主动指定不同的细胞类型，形态发生素的关键性质。梯度的空间范围将在功能上进行检查。最后，为了通过功能丧失研究最大限度地了解DV模式和BMP梯度的产生、调节和作用，识别该途径中的所有遗传参与者至关重要。为此，将分析一个未表征的背侧化突变基因，这可能是该途径的一个新组分。这些研究与人类疾病的研究直接相关，因为该途径中的一些基因已被证明或涉及多种人类疾病状态和人类遗传性疾病的原因。