Endoderm patterning in the mouse embryo

小鼠胚胎中的内胚层模式

• 批准号: RGPIN-2017-04917
• 负责人: Hoodless, Pamela
• 金额: $ 2.04万
• 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: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629057
• 关键词: Endoderm; patterning; mouse; embryo

The definitive endoderm (DE), one of the primary germ layers in the embryo, gives rise to the organs of the respiratory and gastrointestinal tracts, including the epithelial cells of the lungs, stomach, colon, intestine, liver, and pancreas. Considering that these tissues are major sites of health problems, including congenital defects, cancers, and organ malfunctions, we know surprisingly little about the early embryonic development of the DE. This is primarily due to a lack of specific regionally expressed genes that can be used to evaluate DE patterning in the embryo. In screen for novel DE markers, we identified the gene Nephrocan (Nepn) that is exclusively expressed in the midgut of the mouse embryo beginning at gastrulation This genes is the earliest known marker of the midgut endoderm. We are using this gene as a window to understand gut formation and patterning. To that end, we have generated a mouse line in which an inducible version of CRE is under the control of the Nepn promoter. We will use this mouse line to identify the decedents of the midgut lineage and determine the plasticity of the gut endoderm. Moreover, we will probe the role of SOX transcription factors in midgut development.

定形内胚层（DE）是胚胎中的初级胚层之一，产生呼吸道和胃肠道的器官，包括肺、胃、结肠、肠、肝和胰腺的上皮细胞。考虑到这些组织是健康问题的主要部位，包括先天性缺陷，癌症和器官功能障碍，我们对DE的早期胚胎发育知之甚少。这主要是由于缺乏特定的区域表达的基因，可用于评估DE模式在胚胎中。在筛选新的DE标记物时，我们鉴定了从原肠胚形成开始仅在小鼠胚胎中肠中表达的基因Nephrocan（Nepn）。该基因是已知的最早的中肠内胚层标记物。我们正在使用该基因作为了解肠道形成和模式的窗口。为此，我们已经产生了一个小鼠系，其中CRE的诱导型版本是在Nepn启动子的控制下。我们将使用这个小鼠系来识别中肠谱系的死者并确定肠道内胚层的可塑性。此外，我们将探讨SOX转录因子在中肠发育中的作用。