The Lineage of the Midgut Definitive Endoderm

中肠定形内胚层的谱系

• 批准号: 418298-2012
• 负责人: Hoodless, Pamela
• 金额: $ 2.91万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=573575
• 关键词: Lineage; Midgut; Definitive; Endoderm

The early embryo is composed of three types of tissues; the ectoderm will form the brain, nervous system and skin; the mesoderm will form bones, muscles, and organs such as heart, kidneys, ovaries and testis; and endoderm or gut will form tissues of the respiratory and gastrointestinal tract including organs such as lungs, liver, pancreas, intestine and colon. My laboratory is focused on understanding how endoderm develops into the diverse array of organs that comprise the respiratory and gastrointestinal tracts. The endoderm forms a sheet of cells that cover the belly side of the embryo. Through cell-to-cell communication, cells are instructed to form the different organs of the gut in the correct order along the gut tube so that they function normally. Our proposal focuses on the expression and functions of a gene called Nephrocan (Nepn). We have shown that Nepn is exclusively expressed in the midgut region of the embryo that is thought to form the intestine and part of the pancreas. Experiments in the lab have shown that Nepn inhibits a communication pathway known as TGF? suggesting that inhibition of this pathway is required for midgut formation. In our project, we will use the Nepn gene to trace the cells of the midgut to determine their organ fate. We will also examine how the expression of Nepn is restricted to the midgut. Finally, we will determine the functions of Nepn by deleting the gene in the mouse. Together, these experiments will allow us to understand how the midgut forms and the role of Nepn in midgut formation. Many disorders are thought to result from the breakdown of communication pathways that regulate cell functions in the adult and that function during normal development. If we can understand the basic mechanisms that allow tissues develop normally, we may use this information to generate better therapies, such as directing stem cells into tissues that can be used for transplantation.

早期胚胎由三种类型的组织组成；外胚层将形成大脑、神经系统和皮肤；中胚层将形成骨骼、肌肉和器官，如心脏、肾脏、卵巢和睾丸；内胚层或肠道会形成呼吸道和胃肠道的组织，包括肺、肝、胰腺、肠和结肠等器官。我的实验室专注于了解内胚层如何发育成包括呼吸道和胃肠道的各种器官。内胚层是覆盖在胚胎腹部的一层细胞。通过细胞间的交流，细胞被指示沿着肠管以正确的顺序形成肠道的不同器官，从而使它们正常运作。我们的建议集中在一个叫做肾can （Nepn）的基因的表达和功能上。我们已经证明，Nepn仅在胚胎的中肠区域表达，该区域被认为是形成肠道和部分胰腺的区域。实验室实验表明，Nepn抑制一种被称为TGF？这表明抑制该途径是中肠形成所必需的。在我们的项目中，我们将使用Nepn基因来追踪中肠细胞，以确定它们的器官命运。我们还将研究Nepn的表达如何局限于中肠。最后，我们将通过在小鼠中删除Nepn基因来确定其功能。总之，这些实验将使我们了解中肠是如何形成的以及Nepn在中肠形成中的作用。