Genetic and Developmental Mechanisms of a Morphogenetic Program

形态发生程序的遗传和发育机制

• 批准号: 9506844
• 负责人: David Fitch
• 金额: $ 54万
• 依托单位: New York University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9506844&HistoricalAwards=false
• 关键词: Genetic; Developmental; Mechanisms; Morphogenetic; Program

Fitch, David IBN-9506844 To understand how morphological diversity in multicellular animals has arisen by the accumulation of evolutionary changes in genes, an understanding is first required of how morphology is specified by genes and developmental mechanisms. The 4-celled tail tip of the nematode, Caenorhabditis elegans, is being studied as a model for elucidating the genes and developmental processes involved in producing its morphology. Because this structure adopts different morphologies in related species, the tail tip provides a model for the evolution of morphogenesis as well. In C. elegans, the shape of the tail tip is pointy in adult hermaphrodites and blunt in adult males. The pointy shape in hermaphrodites results from retention of the larval state, whereas the blunt shape in males results from cell fusions and changes in cell size, shape and possible adhesion that occur rapidly, just before the last larval molt. Additionally, a cell-cell signalling event may induce the coordinated expression of these events. To identify genes involved in male tail tip morphogenesis, morphological mutants are being isolated and characterized. One such gene, lep-1, acts specifically to control adult fate in male tail tip cells and is being cloned to determine its molecular function and expression pattern. Epistatic interactions among identified genes will eventually be studied. The hypothesized cell-cell interactions in the induction of tail tip morphogenesis are being tested by selective ablation of multiple or single candidate cells with a laser microbeam. Other cellular processes potentially involved in tail tip morphogenesis are being investigated with markers and inhibitors of cellular components. To provide a precise microanatomical framework for these genetic and developmental analyses, the cellular architecture of the tail tip is being detailed by electron microscopy. The major educational activities take the form of undergraduate and graduate courses (mainly on evolution and evolutionary developmental biology), but participation in pre- service teacher education, undergraduate advising, and supervision of high school, undergraduate and graduate student research projects in the laboratory are also important. In the courses and laboratories, emphasis is placed on inquiry-centered, hands-on learning. Students are guided by question-based approaches to construct their own knowledge and skills. In particular activities, cooperature learning is encouraged to develop communication skills and the ability to work collaboratively as well as independently. A continuing emphasis in both coursework and assessment will be the development of language and problem- solving skills. The objectives of all of these activities are to develop in all of the participating students a solid foundation of knowledge in biology, a hearthy skepticism and creative ability to formulate constructive questions and hypothesis (and thus an appreciation of science as an approachable, dynamic, creative, human activity), a practical knowledge of the scientific method as a general problem-solving tool, and an ability to effectively communicate findings and concepts in both oral and written language.

Fitch, David IBN-9506844 为了了解多细胞动物的形态多样性是如何通过基因进化变化的积累而产生的，首先需要了解基因和发育机制如何指定形态。 人们正在研究线虫秀丽隐杆线虫的 4 细胞尾尖，作为阐明其形态产生所涉及的基因和发育过程的模型。 由于这种结构在相关物种中采用了不同的形态，因此尾尖也为形态发生的进化提供了模型。 在秀丽隐杆线虫中，成年雌雄同体的尾尖形状是尖的，成年雄性的尾尖形状是钝的。 雌雄同体的尖形状是由于幼虫状态的保留造成的，而雄性的钝形状是由于细胞融合以及细胞大小、形状和可能的粘附的变化造成的，这些变化发生在最后一次幼虫蜕皮之前。 此外，细胞间信号传导事件可以诱导这些事件的协调表达。 为了鉴定参与雄性尾尖形态发生的基因，正在分离和表征形态突变体。 其中一种基因，lep-1，专门控制雄性尾尖细胞的成体命运，目前正在对其进行克隆以确定其分子功能和表达模式。 最终将研究已识别基因之间的上位相互作用。 正在通过用激光微束选择性消融多个或单个候选细胞来测试在诱导尾尖形态发生中假设的细胞间相互作用。 正在利用细胞成分的标记物和抑制剂来研究可能涉及尾尖形态发生的其他细胞过程。 为了为这些遗传和发育分析提供精确的微观解剖框架，正在通过电子显微镜详细研究尾尖的细胞结构。 主要教育活动采取本科生和研究生课程的形式（主要是进化论和进化发育生物学），但参与职前教师教育、本科生指导以及实验室高中、本科生和研究生研究项目的监督也很重要。 在课程和实验室中，重点放在以探究为中心的实践学习上。 学生通过基于问题的方法来构建自己的知识和技能。 在特定活动中，鼓励合作学习以培养沟通技巧以及协作和独立工作的能力。 课程作业和评估的持续重​​点将是语言和解决问题技能的发展。 所有这些活动的目标是培养所有参与学生扎实的生物学知识基础、提出建设性问题和假设的强烈怀疑精神和创造性能力（从而认识到科学是一种平易近人、动态、创造性的人类活动）、科学方法作为一般问题解决工具的实践知识，以及以口头和书面语言有效交流发现和概念的能力。