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Mechanisms of epithelial remodeling during organ development in C. elegans

线虫器官发育过程中上皮重塑的机制

基本信息

批准号：
10620371
负责人：
JAMES R PRIESS
金额：
$ 22.52万
依托单位：
FRED HUTCHINSON CANCER CENTER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2022-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10620371
关键词：
Mechanisms epithelial remodeling during organ

项目摘要

PROJECT SUMMARY/ABSTRACT One of the fundamental steps in the formation of most organs is the assembly of cells into epithelial layers; simple epithelial cells share a common polarity, are linked by apical junctions and share a basal basement membrane. Epithelial precursors often arise in different parts of the embryo and must aggregate together, often sorting from other types of cells, to form a primordium. Cells within the primordium must then undergo changes in position or shape to create organ morphology. Some remodeling-specific behaviors of normal epithelia cells, such as the loss of adhesion, are reminiscent of cancer cells, the vast majority of which originate from epithelial cells. We want to understand how epithelial cells sort and rearrange, and are studying this in the digestive tract of the nematode C. elegans. C. elegans provides a simple genetic system for investigating basic problems of cell biology, and has had major impact on our understanding of diverse processes such as apoptosis or RNA-mediated gene inhibition. The digestive tract consists primarily of two epithelial tubes, the pharynx and the intestine; we will use the pharyngeal cells to study how precursor cells sort from other cell types, and use the intestine to study how epithelial cells rearrange during organogenesis. Although the pharyngeal precursors cells normally arise from contiguous cells, we demonstrated that they have sorting potential when mixed with other cell types. We want to study the cell biology of sorting in this model, and identify genes required for sorting. Cells at both ends of the intestinal tube undergo a rotation during morphogenesis; we believe this rotation functions to align the lumen throughout the length of the tube. We discovered that the anterior intestinal cells are guided to their new positions by an UNC-6/netrin signaling pathway. This pathway is best understood for its function in nervous system development, but several recent studies have demonstrated that it is also important for the development of non-neural tissues. We want to determine how this pathway functions to reposition the anterior cells, and to determine how cells at the posterior end rotate. Finally, we want to use the powerful genetics of C. elegans to identify genes required for both kinds of epithelial remodeling.

项目总结/摘要大多数器官形成的基本步骤之一是细胞的组装简单的上皮细胞共享一个共同的极性，通过顶端连接，交界处和共享一个基底膜。上皮前体细胞通常出现在胚胎的不同部分，必须聚集在一起，通常是从其他类型中分离出来的。形成原基。然后原基内的细胞必须经历变化在位置或形状上形成器官形态。一些特定的重塑行为正常的上皮细胞，如粘附的丧失，使人联想到癌细胞，其中绝大多数来源于上皮细胞。我们想知道上皮细胞的排序和重新排列，并正在研究这在消化道的线虫C.优雅的C.线虫提供了一个简单的遗传系统，细胞生物学的基本问题，并对我们的理解产生了重大影响不同的过程，如细胞凋亡或RNA介导的基因抑制。消化肠道主要由两个上皮管，咽和肠;我们将使用研究前体细胞如何从其他细胞类型中分选出来，并使用研究上皮细胞在器官发生过程中如何重排。虽然咽前体细胞通常来自相邻的细胞，我们证明，它们在与其它细胞类型混合时具有分选潜力。我们想研究细胞在这个模型中的分选生物学，并确定分选所需的基因。细胞在两个在形态发生过程中，肠管的末端经历旋转;我们认为这是旋转用于在管的整个长度上对准内腔。我们发现前肠细胞被一个β-6/netrin引导到它们的新位置，信号通路这条通路最好的理解是它在神经系统中的功能发展，但最近的几项研究表明，它也很重要，非神经组织的发育。我们想确定这条通路其功能是重新定位前部细胞，并决定后端的细胞如何旋转。最后，我们想利用C的强大遗传学。来识别基因这两种上皮重塑都需要