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: 7541733
• 负责人: DAVID A WEISBLAT
• 金额: $ 27.9万
• 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/7541733
• 关键词: Acute; Ally; Amino Acid Sequence; Animal Model; Animals; Annelida; Arthropods; Brachyury protein; Cell physiology; Cells; Cleaved cell; Comparative Study; Congenital Abnormality; Consensus; Development; Developmental Process; Dorsal; Drosophila genus; Embryo; Embryonic Development; Evolution; Family; Gene Expression; Genes; Genetic Models; 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; Organism; Pathway interactions; Pattern; Peptide Sequence Determination; Phylogenetic Analysis; Phylogeny; Platyhelminths; Play; Principal Investigator; Process; 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; 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; stem cell biology

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 过程允许身体计划的变化的演变。为此，我们比较了 现存的生物体相对于“生命之树”（生命发生），他们出现。之间的比较 不同的生物也应该有助于确定在遗传模型中发现的发育特征 微生物更有可能在人类中运作，并应阐明急性 发育机制紊乱和出生缺陷。 水蛭（环节动物门，分节蠕虫）属于Lophotrochozoa超门， 三组双侧对称的动物在新兴的胚胎发育的基础上比较DMA和 不同物种之间的蛋白质序列散轮虫约占现存门的一半，包括 非无腔扁形虫、软体动物和环节动物。然而，大多数发展中的研究涉及脊椎动物， （超门），线虫或果蝇（都在超门蜕皮动物）。包括 条轮藻种将增加比较发展的广度和力量。水蛭 使用Helobdella是因为它的胚胎是许多Lophotrochozoan物种中研究最好的。它 基因组也很紧凑因此，沿着的还有多毛类蠕虫（Capitella）和软体动物（Lottia）， Helobdella是该部门选择进行全基因组测序的3种Lophotrochozoans之一。美国能源 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。 具体来说，拟议的研究是阐明TGF β通路在早期水蛭 胚胎，使用原位杂交和RT-PCR研究基因表达，加上细胞内注射 谱系示踪剂和mRNA或反义mopholino寡聚体，以比较正常胚胎中的细胞命运， 那些TGF β通路被破坏的细胞。拟议的实验将有助于 了解TGFb信号如何在果蝇中指定背侧命运，而在脊椎动物中指定腹侧命运。他们 也有助于理解上皮细胞向间质细胞转化的细胞过程 EMTs在正常发育和癌症转移中起关键作用。