Positional identity in the zebrafish embryo

斑马鱼胚胎中的位置同一性

• 批准号: 7931094
• 负责人: DAVID J. GRUNWALD
• 金额: $ 8.94万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2010-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7931094
• 关键词: Positional; identity; zebrafish; embryo

DESCRIPTION (provided by applicant): During vertebrate development, the embryo is subdivided into domains that correlate with eventual specializations in cellular function. The regional expression and function of multiple transcription factors, acting antagonistically and in concert, define unique identities for these domains. Complex interactions among these transcription factors regulate cellular and molecular events that are unique to each tissue. Discovering how positional control of genetic networks leads to cellular form and function is an important step towards understanding the mechanisms underlying human birth defects and disease. The investigators collaborating in this program project have a history of common scientific interests and approaches, all using the zebrafish, a vertebrate model organism particularly suited to genetic, molecular, and embryonic manipulations. The three interrelated component projects will address a common theme: how do particular regulatory genes act to control region-specific cell differentiation? All three projects share a common focus on the roles of transcription factors, especially members of the T-box protein family, asking: what are the required roles of these genes? How is their expression controlled? And, how do combinations of transcription factors act together to regulate downstream effector genes that execute position-specific functions? Each project will study the patterning of a different tissue: the mesoderm germ layer; Kupffer's vesicle, a source of left-right patterning; and the dorsal retina. Comparing results among these systems will allow us to search for general principles by which transcription factors or effector genes act together, as well as to ask whether specific molecular interactions are common to different tissues. In addition to this intellectual synergy, this application will provide common resources to allow cooperation on large-scale experiments that were impossible for each group alone. A Zebrafish Genetics Core Facility will house existing wild-type and mutant fish, generate animals for genetic screens, and provide resources for phenotype analyses. A Molecular Analysis Core Facility will perform sequence-based screening of mutagenized genomes (TILLING), genotyping of identified mutants, and gene expression analysis by semi-automated in situ hybridization. Through interactions between the projects and using the core units, this program will identify new components of the molecular pathways that regulate fundamental steps in vertebrate tissue patterning, discover effector genes that allow cells to express position-specific fates and behaviors, and start to dissect the genetic networks that control positional identity during development.

描述（由申请人提供）：在脊椎动物发育期间，将胚胎细分为与最终在细胞功能方面的专业相关的域。多种转录因子的区域表达和功能，以拮抗和协同作用，定义了这些领域的独特身份。这些转录因子之间的复杂相互作用调节每个组织独有的细胞和分子事件。发现遗传网络的位置控制如何导致细胞形式和功能是理解人类先天缺陷和疾病基础机制的重要步骤。在该计划项目中合作的研究人员具有共同的科学利益和方法的历史，所有这些都使用斑马鱼，斑马鱼是一种脊椎动物模型有机体，特别适合遗传，分子和胚胎操纵。三个相互关联的组件项目将解决一个共同的主题：特定的调节基因如何控制特定区域的细胞分化？这三个项目都共同关注转录因子的作用，尤其是T-box蛋白家族的成员，问：这些基因所需的作用是什么？他们的表达如何控制？而且，转录因子的组合如何共同作用以调节执行特定位置功能的下游效应基因？每个项目将研究不同组织的模式：中胚层生殖层；库普弗的囊泡，左右图案的来源；和背视网膜。比较这些系统之间的结果将使我们能够搜索转录因子或效应基因一起起作用的一般原则，并询问特定的分子相互作用是否对不同组织是共同的。除了这种智力协同作用外，该应用程序还将提供共同的资源，以便在每个小组不可能进行的大规模实验上进行合作。斑马鱼遗传学核心设施将容纳现有的野生型和突变鱼，为遗传筛查产生动物，并为表型分析提供资源。分子分析核心设施将对诱变基因组（耕种），鉴定突变体的基因分型进行基于序列的筛选以及通过半自动的原位杂交进行基因表达分析。通过项目与使用核心单元之间的相互作用，该程序将确定分子途径的新组成部分，这些组分是调节脊椎动物组织模式的基本步骤，发现效应基因，使细胞能够表达位置特异性的命运和行为，并开始剖析在发育过程中控制位置的遗传网络。