CELL CELL ADHESION MOLECULES IN PANCREATIC ISLETS ONTOGENY & FUNCTION

背景：组织发生和器官发生被认为是 由程序化的细胞-细胞和细胞-基质相互作用指导。 细胞间的粘附性由特定的细胞粘附性决定 分子(CAM)，其模块化表达也被认为调节 细胞增殖和/或分化。的一个重要特点 CAM是它们受发育调节的表达，似乎 在组织发生和器官发生过程中起着重要作用 组织包括胰腺。它们的细胞类型特异性表达 因此可以用来识别处于特定阶段的细胞群 关于发展的问题。此外，还需要凸轮来维护 组织结构，这反过来又对器官的功能至关重要。 事实上，我们之前已经证明了黏附分子 因为NCAM都参与了三维空间的维护 具有胰岛素分泌细胞的胰岛细胞的组织 位于核心，其他内分泌细胞类型(？和 PP，分泌胰升糖素、生长抑素和胰多肽， 分别设置在外围。这个奇特的胰岛细胞 类型分离在糖尿病中受到干扰，这表明这种 可能需要配置才能正常发挥胰岛功能。 目标：我们目前的工作重点是识别和 细胞间黏附分子参与人类个体发育的功能特征 胰岛。过去一年成绩摘要： 实验是为了识别细胞间的黏附分子。 (CaM)由胎儿胰腺细胞表达，并了解其 细胞间黏附、增殖和内分泌的功能作用 差异化。特别是，我们已经将EpCAM确定为主要的 胰腺上皮细胞-细胞黏附的介体。有趣的是， 这种细胞黏附分子似乎参与了上皮细胞的生长。部分 这项工作需要使用共焦显微镜和IVEM在 NCMIR。这些数据是一份正在准备的手稿的主题(1)。 此外，根据我们以前的经验表明，一个重要的 间充质来源的生长因子如HGF/SF在血管内皮细胞生长中的作用 人胎胰腺细胞的增殖，我们已经研究了 HGF/SF C-MET受体在人体内的表达模式 胎儿和成人生命中的胰腺。这些实验有 确定C-MET仅限于上皮间室 发育中的人类胰腺，它主要是 成人内分泌细胞(朗格汉斯胰岛)的表达 胰腺(2例)。最后，我们寻找内分泌的标记物 分化导致GAD65(谷氨酸)的鉴定 脱羧酶，65kD)在上皮细胞内进入 内分泌分化(即胰岛素和/或胰升糖素的表达)。 这项研究最近也被接受出版(3)。

Background: Histogenesis and organogenesis is believed to be directed by programmed cell-cell and cell-to-matrix interactions. Cell-cell adhesiveness is determined by specific cell adhesion molecules (CAMs), whose modular expression is also thought to regulate cell proliferation and/or differentiation. An important feature of CAMs is their developmentally regulated expression which appears to play important roles during histogenesis and organogenesis of various tissues including the pancreas. Their cell type-specific expression may therefore be used to identify cell populations at defined stages of development. Furthermore, CAMs are required for the maintenance of tissue architecture, which in turn is critical to organs' function. In fact, we have previously demonstrated that adhesion molecules such as NCAM are involved in the maintenance of the three-dimensional organization of pancreatic islet cells, with insulin-secreting ?-cells located in the core, and the other endocrine cell t ypes (??????and pp, secreting glucagon, somatostatin and pancreatic polypeptide, respectively??arranged at the periphery. This peculiar islet cell type segregation is perturbed in diabetes suggesting that such a configuration might be necessary for proper islet function. Objectives: Our current efforts focus on the identification and functional characterization of CAMs involved in the ontogeny of human pancreatic islets. Summary of the past year achievements: Experiments were designed to identify cell-cell adhesion molecules (CAMs) expressed by fetal pancreatic cells, and to understand their functional role in cell-cell adhesion, proliferation, and endocrine differentiation. In particular, we have identified EpCAM as a major mediator of pancreatic epithelial cell-cell adhesion. Interestingly, this CAM appeared to be involved in epithelial cell growth. Part of this work entailed use of the confocal microscope and the IVEM at the NCMIR. These data are the subject of a manuscript in preparation (1). In addition, based on our previous experience suggesting an important role of mesenchyme-derived growth factors such as HGF/SF in proliferation of human fetal pancreatic cells, we have examined the expression pattern of the C-MET receptor for HGF/SF within the human pancreas both in fetal and adult life. These eperiments have determined that C-MET is restricted to the epithelial compartment of the developping human pancreas, and that it becomes predominantly expressed on endocrine cells (islets of Langerhans) in the adult pancreas (2). Finally, our search for markers of endocrine differentiation led to the identification of GAD65 (Glutamic Acid Decarboxylase, 65kD) within epithelial cells entering the pathway of endocrine differentiatrion (i.e. insulin and/or glucagon expression). This study has also been recently accepted for publication (3).