Genetic Control of Segmentation

分割的遗传控制

基本信息

批准号：
8049416
负责人：
SUSAN J. BROWN
金额：
$ 1.55万
依托单位：
KANSAS STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2010-09-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The clock and wavefront mechanisms underlying segmentation in vertebrates and the genetic hierarchy regulating segmentation in Drosophila seemingly imply independent origins of metameric development. However, comparative studies in non-drosophilid insects and other arthropods provide increasing molecular evidence for a common ancestry. In Drosophila, segments are patterned simultaneously. In most other insects including the red flour beetle Tribolium castaneum, other arthropods and vertebrates, segmentation is a longer process that occurs progressively from anterior to posterior. To understand the molecular mechanisms driving sequential metamerism and identify new genes important to this process, we are studying the genetic regulation of segmentation in Tribolium. In Tribolium, abdominal segments arise from a posterior growth zone during germband elongation, and RNAi with several early patterning genes truncates segmentation from the growth zone, suggesting this is an important regulation point. We have identified a gene circuit of primary pair-rule genes that functions to generate segments sequentially. Defects in its components disrupt the gene circuit and truncate the segmentation process. Periodic expression of two genes in this circuit initiates as twin spots in the posterior growth zone and may be regulated by early patterning genes. In addition, we have found that TcWnt8 is expressed in twin spots in the posterior growth zone, and TcWnt8 RNAi embryos are truncated in the thorax. We hypothesize that segmentation and elongation may be regulated by posterior signals that control components of the pair-rule gene circuit and/or proliferation. We will combine genetic and molecular approaches to analyze the relationship of cell proliferation, convergent extension and posterior signaling to segmentation, all of which are fundamental to embryonic elongation in vertebrates and arthropods. The genetic and genomic tools we have developed, combined with the Tribolium genome sequence, provide a unique opportunity to identify, regulatory genes and molecular processes which may represent presently unrecognized, developmentally significant mammalian counterparts important to segmentation. Our studies have the potential to provide new insight into human birth defects in spinal development and cancers related to misregulation of signaling mechanisms.

描述（由申请人提供）：脊椎动物的分割的时钟和波前机制以及果蝇中调节分割的遗传层次结构似乎意味着跨化发育的独立起源。然而，在非嗜血芽孢昆虫和其他节肢动物中的比较研究为共同血统提供了越来越多的分子证据。在果蝇中，段是同时进行图案化的。在大多数其他昆虫中，包括红粉甲虫triborium castaneum，其他节肢动物和脊椎动物，分割是一个较长的过程，从前到后逐渐发生。为了了解驱动顺序变质的分子机制并确定对这一过程重要的新基因，我们正在研究贡献的遗传调节。在Tribolium中，腹部片段是由生长延伸过程中的后生长带产生的，而RNAi具有几个早期构图基因的RNAi，可截断从生长带的分割，这表明这是一个重要的调节点。我们已经确定了一个基本成对规则基因的基因回路，该基因依次生成段。其组分中的缺陷破坏了基因电路并截断了分割过程。该电路中两个基因的周期性表达启动为后生长带的双斑，可以通过早期模式基因调节。此外，我们发现TCWNT8在后生长区的双点中表达，TCWNT8 RNAi胚胎在胸腔中被截断。我们假设分割和伸长可以通过控制配对基因回路和/或增殖的后部信号来调节。我们将结合遗传和分子方法，以分析细胞增殖，收敛延伸和后验信号与分割的关系，所有这些都对脊椎动物和节肢动物中的胚胎伸长至关重要。我们开发的遗传和基因组工具与贡献基因组序列相结合，为识别，调节基因和分子过程提供了一个独特的机会，这些机会可能代表目前未识别的，发育意义上的哺乳动物对分割重要的哺乳动物对应物。我们的研究有可能对脊柱发育中人类出生缺陷的新见解以及与信号传导机制不正调有关的癌症。