CAREER: Forces Underlying Germ Band Retraction in Drosophila Embryogenesis

职业：果蝇胚胎发生中种带回缩的潜在力量

• 批准号: 0545679
• 负责人: Michael Hutson
• 金额: $ 83.28万
• 依托单位: Vanderbilt University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0545679&HistoricalAwards=false
• 关键词: CAREER; Forces; Underlying; Germ; Band

INTELLECTUAL MERITAlthough the body plan of a developing embryo is ultimately determined by its genetic program, the proximate cause of morphogenesis is the generation and regulation of intercellular forces. Genetic approaches to development have been hugely successful, particularly in regard to the genes that determine patterns of cell-fate determination. However, additional genes then determine the mechanical consequences of cell-fate decisions. To unambiguously determine the role of these genes from mutant morphological phenotypes, it is crucial to quantitatively understand the forces underlying morphogenesis. In that spirit, this project involves experimental and computational investigations of the forces underlying the morphogenetic event of germ-band retraction in the fruit fly, Drosophila melanogaster. A working model for germ-band retraction will be experimentally challenged through laser-microsurgery and computational modeling. The working model is based on distinct roles for each of three tissues. These roles are embodied in the following hypotheses: (i) germ-band retraction is driven by spatially and temporally regulated contraction of the amnioserosa; (ii) the germ band itself responds passively to tension in the amnioserosa; and (iii) the distribution of tension in the amnioserosa is determined by contact between the amnioserosa and yolk sac. In light of these hypotheses, the specific goals of this project are:1. To delineate the physical role of the amnioserosa in germ-band retraction (GBR), including the spatial and temporal limitations of this role.2. To determine if there is an active component to the cell shape changes observed in the retracting germ band.3. To quantitatively map and model the forces underlying GBR with high spatial and temporal resolution.4. To link mutant GBR-failure phenotypes to defects in the underlying forces.Note that these goals complement traditional genetic approaches to Drosophila embryogenesis. By focusing on a model organism for which a vast array of genetic techniques are available, the results of this research will provide much-needed leverage, enabling this and future investigations to better connect morphogenesis to the genetic program of development.BROADER IMPACTSIntegral to success in the research goals stated above, the PI's educational plan will enable and encourage students from both physics and biology to work across the disciplinary divide. The four main thrusts of this plan are: (i) to improve the physics education of undergraduate life-science majors by implementing best practices from physics-education research; (ii) to provide interdisciplinary research opportunities for undergraduates; (iii) to recruit under-represented minorities into biophysical research through a partnership with Fisk University, a local HBCU, and (iv) to develop an interdisciplinary graduate course for physical scientists that stresses the ability to communicate complex ideas across disciplinary lines. The major broader impact of these integrated educational activities will be to strengthen interdisciplinary research, both by preparing students to work across the physics/biology interface and by increasing the appreciation of biophysics within the physics and biology mainstreams. Furthermore, the research project provides a new perspective on an exceedingly well-studied system. By defining the mechanical aspects of a major step in Drosophila embryogenesis, this research will build new intellectual infrastructure. It will enable the large community of researchers working on this problem to ask an entirely new set of questions. In addition, the software tools developed in this project (both for image processing and for analyzing the intrinsic forces using laser hole-drilling techniques) will be disseminated broadly to the Drosophila research community.

智力优势尽管发育中的胚胎的体型最终是由其遗传程序决定的，但形态发生的直接原因是细胞间力的产生和调节。 遗传学的发展方法取得了巨大的成功，特别是在决定细胞命运模式的基因方面。 然而，其他基因则决定了细胞命运决定的机械后果。 为了明确地确定这些基因在突变体形态表型中的作用，定量地了解形态发生背后的力量至关重要。 在这种精神下，这个项目涉及实验和计算的力量，在果蝇的胚带收缩的形态发生事件的调查，果蝇。 生殖带收缩的工作模型将通过激光显微手术和计算建模进行实验挑战。 工作模型基于三种组织中每一种的不同作用。 这些作用体现在以下假设中：（i）胚带收缩是由浆膜的空间和时间调节收缩驱动的;（ii）胚带本身被动地响应浆膜的张力;（iii）浆膜和卵黄囊之间的接触决定浆膜张力的分布。 根据这些假设，本项目的具体目标是：1。 描述羊水在胚带回缩（GBR）中的物理作用，包括该作用的空间和时间限制。2. 以确定是否有一个积极的组成部分，以观察到的细胞形状的变化，在收回胚芽带。 以高的空间和时间分辨率定量映射和建模GBR的潜在力量. 将突变的GBR失败表型与潜在力的缺陷联系起来。注意这些目标补充了果蝇胚胎发生的传统遗传学方法。 通过专注于一个模式生物，其中大量的遗传技术是可用的，这项研究的结果将提供急需的杠杆作用，使这项和未来的调查，以更好地连接形态发生的遗传程序的发展。PI的教育计划将使物理学和生物学的学生能够并鼓励他们跨越学科鸿沟。 该计划的四个主要目标是：（i）通过实施物理教育研究的最佳实践来改善本科生命科学专业的物理教育;（ii）为本科生提供跨学科研究的机会;通过与当地的一个HBCU-菲斯克大学合作，招募代表性不足的少数群体参与生物物理研究，以及（iv）为物理科学家开发跨学科研究生课程，强调跨学科交流复杂思想的能力。 这些综合教育活动的主要影响将是加强跨学科研究，既通过培养学生跨物理/生物学接口的工作，并通过增加物理学和生物学主流内的生物物理学的升值。 此外，该研究项目提供了一个非常好的研究系统的新视角。 通过定义果蝇胚胎发育中一个重要步骤的机械方面，这项研究将建立新的智力基础设施。 它将使研究这个问题的广大研究人员能够提出一系列全新的问题。 此外，该项目开发的软件工具（用于图像处理和使用激光钻孔技术分析内力）将广泛传播给果蝇研究界。