The Lineage of the Midgut Definitive Endoderm

早期胚胎由三种组织组成：外胚层形成大脑、神经系统和皮肤；中胚层形成骨骼、肌肉和心脏、肾脏、卵巢和睾丸等器官；内胚层或肠道形成呼吸道和胃肠道组织，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组成呼吸道和胃肠道的各种器官阵列。内胚层形成一层覆盖在胚胎腹部的细胞。通过细胞间的通讯，细胞被指示沿着肠管以正确的顺序形成肠道的不同器官，以便它们正常运作。我们的研究重点是一种名为Nephrocan(NEPN)的基因的表达和功能。我们已经证明，NEPN只在胚胎的中肠区域表达，该区域被认为是形成肠道和胰腺的一部分。实验室实验表明，NEPN抑制一种称为转化生长因子？的通讯途径。这表明抑制这一途径对于中肠的形成是必要的。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是如何限制在中肠表达的。最后，我们将通过在小鼠中删除该基因来确定NEPN的功能。总之，这些实验将使我们能够了解中肠是如何形成的，以及NEPN在中肠形成中的作用。

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.