TGF-beta and axis formation in Helobdella, a lophotrochozoan

描述(由申请人提供)：PI途中研究的长期目标是了解发育过程规则的变化如何允许身体计划的变化。为此，我们将现存生物的发展与它们产生的“生命树”(系统发育)进行比较。不同生物之间的比较也应该有助于确定在遗传模式生物中发现的哪些发育特征更有可能在人类身上发挥作用，并应该揭示发育机制的剧烈扰动与出生缺陷之间的联系。根据物种间DNA和蛋白质序列的比较，水蚤(节段虫，环节动物门)属于Lophotrochozoa超门，是新出现的系统发育中三类两侧对称的动物之一。Lophotrochozoa包括大约一半现存的门，包括非扁虫、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(后口门超级门)、线虫或果蝇(两者都属于蜕皮虫门)。包括轮虫物种将增加比较发展的广度和力量。之所以使用水蚤Helobdella，是因为它的胚胎是许多轮虫物种中研究得最好的。它也有一个紧凑的基因组。因此，与多毛类蠕虫(Capitella)和软体动物(Lottia)一起，Helobdella是国防部选择进行全基因组测序的3种轮虫之一。能源联合基因组研究所的。这三个物种内部和之间的协同发展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，这项研究是为了阐明转化生长因子β途径在水蛭早期胚胎中的作用(S)，使用原位杂交和RT-PCR来研究基因表达，并在细胞内注射谱系示踪物和mRNAs或反义吗啉寡聚物，以比较正常胚胎和转化生长因子途径被破坏的胚胎中的细胞命运。拟议的实验将有助于理解转化生长因子信号如何决定果蝇的背部命运，而不是脊椎动物的腹面命运。他们还将有助于理解被称为上皮向间充质转化(EMTs)的细胞过程，EMTs在正常发育和癌症转移中都发挥着关键作用。

DESCRIPTION (provided by applicant): The long term objective of the PI en route'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 DNA 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 or fruitfly (both in the superphylum 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 TGF¿ 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 morpholino oligomers to compare cell fates in normal embryos with those where the TGF¿ pathways have been disrupted. The proposed experiments will contribute to understanding how TGF¿ 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.