Mechanisms in Developmental Timing

发育时间机制

• 批准号: 0641677
• 负责人: Eric Moss
• 金额: --
• 依托单位: Rowan University School of Osteopathic Medicine
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-15 至 2010-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0641677&HistoricalAwards=false
• 关键词: Mechanisms; Developmental; Timing

Intellectual merit: This proposal aims to understand fundamental molecular mechanisms involved in developmental timing, the process that coordinates the synchrony and synchronization of tissue and organ formation. The experimental model is the nematode Caenorhabditis elegans where a number of genes are known to control the succession of events during the animal's larval stages. One of these genes, lin-28, is especially of interest because its homologs in mammals and other animals display precisely timed developmental expression, suggesting it is a conserved timing regulator in diverse animal species. Mutants defective in lin-28 skip developmental events specific to the second larval stage in many tissues, and later events occur precociously. Evidence now suggests that lin-28 opposes the activity of microRNAs (a newly-discovered class of small RNA regulators) and another heterochronic gene, lin-46, in the regulation of hbl-1. hbl-1 is a homologue of fly developmental transcription factor Hunchback and has an important role in controlling cell fates. lin-28 encodes a protein that acts on mRNA. The hypothesis to be tested is that the LIN-28 protein binds the hbl-1 mRNA and inhibits its repression by blocking the action of the miRNAs. The experiments will test whether lin-28 controls hbl-1 expression through its 3' UTR to control developmental timing.Broader impacts: The research will be performed by high school students, undergraduates, and doctoral candidates. The project will be conducted at an institution without an undergraduate population, therefore undergraduate students will be recruited from around the Philadelphia/Camden region to participate the research. High school students will spend afternoons working on independent aspects of the project in preparation for science fairs. The PI is committed to reaching underserved and underprivileged individuals for these opportunities. Doctoral candidates will present their findings at international scientific conferences. All strains and reagents generated will be shared freely with other investigators.

智力优点：该提案旨在了解参与发育时序的基本分子机制，协调组织和器官形成的同步和同步的过程。实验模型是线虫秀丽隐杆线虫，其中已知许多基因控制动物幼虫阶段的事件顺序。其中一个基因lin-28特别令人感兴趣，因为它在哺乳动物和其他动物中的同源物显示出精确的发育表达时间，这表明它是不同动物物种中保守的时间调节因子。lin-28缺陷的突变体跳过了许多组织中第二幼虫阶段特有的发育事件，并且随后的事件早熟发生。现在有证据表明，lin-28对抗microRNA（一类新发现的小RNA调节因子）和另一种异时基因lin-46在hBL-1调节中的活性。hbl-1是果蝇发育转录因子Hunchback的同源物，在控制细胞命运中具有重要作用。lin-28编码作用于mRNA的蛋白质。待检验的假设是LIN-28蛋白结合hbl-1 mRNA并通过阻断miRNA的作用来抑制其抑制。实验将测试lin-28是否通过其3' UTR控制hbl-1的表达来控制发育时间。更广泛的影响：这项研究将由高中生、本科生和博士生进行。该项目将在一个没有本科生的机构进行，因此将从费城/卡姆登地区招募本科生参加研究。高中生将花下午的时间研究该项目的独立方面，为科学博览会做准备。PI致力于为服务不足和弱势群体提供这些机会。博士候选人将在国际科学会议上介绍他们的研究结果。生成的所有菌株和试剂将与其他研究者免费共享。