Evolution of Axial Patterning - Functional Approaches

轴向图案的演变 - 函数方法

• 批准号: 6836068
• 负责人: PATRICIA N LEE
• 金额: $ 4.83万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-16 至 2006-07-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6836068
• 关键词: Evolution; Axial; Patterning; Functional; Approaches

GOALS FOR FELLOWSHIP TRAINING AND CAREER My dissertation research employed a descriptive approach to a biological question, cloning key developmental regulatory genes and examining their expression patterns to infer developmental functions. The project I am proposing with Dr. Martindale is very different from my graduate training as it will take a functional approach to questions about the evolution of basic metazoan developmental programs. I will propose testable hypotheses and use new experimental approaches to manipulate and investigate gene function in vivo. This will require more sophisticated intellectual approaches to the question, and will utilize modern molecular techniques, including RNAi, morpholinos, ectopic expression, and microinjection. An NRSA Postdoctoral Fellowship will provide me with an invaluable research- and career- development opportunity under the mentorship of Dr. Martindale, one of the foremost experts in evolutionary developmental biology. It will greatly advance my development as a well-rounded research scientist toward my ultimate career objective of becoming a productive faculty member at a university with a strong research [)ro_ram. / / li']iF1"]i 19. NAMEANDDEGREE(S) Mark Q. Martindale, B.A., Ph.D. 20. POSITION/RANK Associate Professor 21. RESEARCH INTERESTS/AREAS Cellular, molecular, and evolutionary aspects of pattern formation ] -[,,_ ,-f,i .]r=.l = ms .] =r*l ¿r*'[._*_ 22. DESCRIPTION (Do not exceed space provided) The objective of this research is to investigate functions of key regulatory genes in axial regionalization during development of multicellular animals. This objective falls within the long-range comprehensive goal of addressing fundamental questions of molecular patterning mechanisms in metazoans. In this study, we will use functional genetic assays to determine the roles of the Hox/ParaHox genes in axial patterning in cnidarians. The conserved function of Hox/ParaHox genes in anterioposterior patterning of triploblastic animals defines the bilaterian 'zootype'. Whether these genes perform comparable roles in cnidarians remains to be determined. There are several specific aims in this proposed study. First, a posterior ParaHox gene will be isolated from Nematostella vectensis (Cnidaria: Anthozoa) and its expression 3attern characterized. Next, the function of cnidarian Hox/ParaHox genes during development will be examined in N. vectensis using two complementary functional assays, ectopic gene expression and gene silencing. Finally, the function of cnidarian Hox/ParaHox genes during the process of regeneration will be examined to elucidate potential homology between the mechanistic events in ontogeny and regeneration. Determining HoxParaHox gene function in cnidarians will allow us to establish axial homologies between cnidarians and bilaterians. These results will reveal the ancestral roles of Hoxand ParaHox genes in early metazoan history and will provide valuable insight to the evolution of complex body plans. PHS 416-1 (Rev. 12/98) Form Page 2 BB CC NAME (Last, first, middle initial) Individual NRSA Application Table of Contents ========================================Section End===========================================

奖学金培训和职业目标 我的论文研究采用描述性方法来解决生物学问题，克隆关键的发育调节基因并检查它们的表达模式以推断发育功能。我与马丁代尔博士一起提出的项目与我的研究生培训非常不同，因为它将采用功能性方法来解决有关基本后生动物发育程序的进化问题。我将提出可检验的假设，并使用新的实验方法来操纵和研究体内基因功能。这将需要更复杂的智力方法来解决这个问题，并将利用现代分子技术，包括 RNAi、吗啉、异位表达和显微注射。 NRSA 博士后奖学金将为我在进化发育生物学领域最重要的专家之一 Martindale 博士的指导下提供宝贵的研究和职业发展机会。它将极大地促进我作为一名全面的研究科学家的发展，实现我的最终职业目标，即成为一所拥有强大研究能力的大学的一名富有成效的教员[)ro_ram。 // li']iF1"]i 19. 姓名和学位 Mark Q. Martindale, B.A., Ph.D. 20. 职位/级别 副教授 21. 研究兴趣/领域 模式形成的细胞、分子和进化方面 ] -[,,_ ,-f,i .]r=.l = ms .] =r*l ¿r*'[._*_ 22. 描述（不要超出提供的空间） 本研究的目的是研究多细胞动物发育过程中轴向区域化关键调控基因的功能。这一目标属于解决后生动物分子模式机制基本问题的长期综合目标。在本研究中，我们将使用功能遗传测定来确定 Hox/ParaHox 基因在刺胞动物轴向模式中的作用。 Hox/ParaHox基因的保守功能 三叶细胞动物的前后模式定义了两侧对称动物的“动物型”。这些基因在刺胞动物中是否发挥类似的作用仍有待确定。这项拟议的研究有几个具体目标。首先，将从 Nematostella vectensis（刺胞动物门：Anthozoa）中分离出后部 ParaHox 基因，并对其表达模式进行表征。接下来是刺胞动物的功能 将使用两种互补的功能检测（异位基因表达和基因沉默）在 N. vectensis 中检查发育过程中的 Hox/ParaHox 基因。最后，将检查刺胞动物Hox/ParaHox基因在再生过程中的功能，以阐明个体发育和再生的机制事件之间的潜在同源性。确定刺胞动物中的 HoxParaHox 基因功能将使我们能够建立轴向 刺胞动物和两侧对称动物之间的同源性。这些结果将揭示 Hox 和 ParaHox 基因在早期后生动物历史中的祖先作用，并将为复杂身体计划的进化提供有价值的见解。 PHS 416-1（修订版 12/98）表格第 2 页 BB CC 名称（姓氏、名字、中间名首字母） 个人 NRSA 申请目录 =========================================章节结束==============================================