TGF-beta and axis formation in Helobdella, a lophotrochozoan

轮轮动物 Helobdella 中的 TGF-β 和轴形成

• 批准号: 7336762
• 负责人: DAVID A WEISBLAT
• 金额: $ 27.99万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7336762
• 关键词: Acute; Ally; Amino Acid Sequence; Animal Model; Animals; Annelida; Arthropods; Brachyury protein; Cell physiology; Cells; Cellular biology; Cleaved cell; Comparative Study; Condition; Congenital Abnormality; Consensus; Development; Developmental Process; Dorsal; Drosophila genus; Embryo; Embryonic Development; Evolution; Family; Gene Expression; Genes; Genetic; Genome; Genomics; Goals; Homologous Gene; Human; In Situ Hybridization; Inhibin-beta Subunits; Injection of therapeutic agent; Institutes; Investigation; Joints; Juglans; Laboratories; Leeches; Life; Ligands; Light; Link; Molecular; Morphology; Natural regeneration; Nematoda; Neoplasm Metastasis; Numbers; Organism; Pathway interactions; Pattern; Peptide Sequence Determination; Phylogenetic Analysis; Phylogeny; Platyhelminths; Play; Principal Investigator; Process; Purpose; Range; Recording of previous events; Recruitment Activity; Regulation; Research; Reverse Transcriptase Polymerase Chain Reaction; Role; Sampling; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Specific qualifier value; Staging; Stem cells; Study models; System; Taxon; Tracer; Transforming Growth Factor beta; Trees; Vertebrates; Work; base; cell behavior; chordin; comparative; epithelial to mesenchymal transition; falls; genome sequencing; insight; precursor cell; programs; research study

The long term objective of the Pi's research is to understand how changes in the regulation of developmental processes permit the evolution of changes in body plan. For this purpose, we compare the development of extant organisms with respect to the "tree of life" (phylogeny) by which they arose. Comparisons between diverse organisms should also help to determine which developmental features discovered in genetic model organisms are more likely to be operating in human, and should shed light on the links between acute perturbations of developmental mechanisms and birth defects. Leeches (segmented worms, phylum Annelida) belong to the super-phylum Lophotrochozoa, one of three groups of bilaterally symmetric animals in the emerging phylogeny based on comparisons of DMA and protein sequences between species. Lophotrochozoa includes roughly half of the extant phyla, including non-acoel flatworms, molluscs and annelids. However, most research in development concerns vertebrates (super-phylum Deuterostomia), nematode orfruitfly (both in the superpylum Ecdysozoa). Including lophotrochozoan species will increase the breadth and power of comparative development. The leech Helobdella is used because its embryo is among the best studied of the many lophotrochozoan species. It also has a compact genome. As a result, along with a polychaete worm (Capitella) and a mollusc (Lottia), Helobdella is one of 3 lophotrochozoans selected for whole genome sequencing by the Dept. of Energy's Joint Genome Institute. Synergistic developmental and genomic analyses within and among these 3 species will help to understand the links between genomic and developmental change. Specifically, the proposed research is to elucidate the role(s) of the TGFb pathway in the early leech embryo, using in situ hybridization and RT-PCR to study gene expression, plus intracellular injection of lineage tracers and mRNAs or anti-sense mopholino oligomers to compare cell fates in normal embryos with those where the TGFb pathways have been disrupted. The proposed experiments will contribute to understanding how TGFb signaling specifies dorsal fates in Drosophila, but ventral fates in vertebrates. They will also contribute to understanding the cellular processes known as epithelial-to-mesenchymal transitions (EMTs), which play a critical role both in normal development and in cancer metastasis.

PI研究的长期目标是了解发育调节的变化 程序允许身体计划中的变化演变。为此，我们比较了两种模式的发展 现存的生物与它们产生的“生命树”(系统发育)有关。比较以下几种情况 不同的生物体也应该有助于确定在遗传模型中发现的哪些发育特征 生物体更有可能在人类体内运行，应该能阐明急性呼吸道感染之间的联系 发育机制的紊乱和出生缺陷。 水蚤(节节线虫，环节动物门)属于线虫超门，是 基于DMA和DMA比较的新系统发育中的三组双侧对称动物 物种间的蛋白质序列。Lophotrochozoa包括大约一半现存的门，包括 非扁形蠕虫、软体动物和环节动物。然而，大多数发展中的研究都与脊椎动物有关 (后口超级门)，线虫或果蝇(都在超级斑节动物中)。包括 轮虫物种将增加比较发展的广度和力量。水蛭 之所以使用Helobdella，是因为它的胚胎是许多轮虫物种中研究最好的之一。它 也有一个紧凑的基因组。结果，与多毛类蠕虫(Capitella)和软体动物(Lottia)一起， Helobdella是美国国防部选择进行全基因组测序的3种轮虫之一。能源部 联合基因组研究所。这3个物种内部和之间的协同发育和基因组分析 将有助于理解基因组和发育变化之间的联系。 具体地说，拟议的研究是为了阐明转化生长因子b通路在早期水蚤中的作用(S)。 胚胎，用原位杂交和RT-PCR研究基因表达，外加细胞内注射 谱系示踪剂和mRNAs或反义mopholino寡聚体比较正常胚胎和 那些TGFb通路被扰乱的地方。拟议的实验将有助于 了解TGFb信号如何决定果蝇的背部命运，而脊椎动物的腹面命运。他们 也将有助于理解被称为上皮向间充质转化的细胞过程 (EMT)，它们在正常发育和癌症转移中都发挥着关键作用。