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-细胞粘附是由特异性细胞粘附决定的 分子（CAM），其模块化表达也被认为是调节 细胞增殖和/或分化。 的重要特征 CAM是它们的发育调节表达， 在各种组织发生和器官发生过程中发挥重要作用 包括胰腺在内的组织。 它们的细胞类型特异性表达 因此可用于鉴定处于确定阶段的细胞群 发展质量和 此外，还需要CAM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，我们以前已经证明，粘附分子，如 由于NCAM参与维护三维 胰岛细胞的组织，与胰岛素分泌？细胞 位于核心，其他内分泌细胞类型（？和 pp，分泌胰高血糖素、生长抑素和胰多肽， 分别？布置在外围。 这个特殊的胰岛细胞 型分离在糖尿病中受到干扰，这表明 配置可能是必要的适当胰岛功能。 目标：我们目前的工作重点是确定和 参与人类个体发育的CAM的功能表征 胰岛 总结过去一年的成就： 设计实验以鉴定细胞间粘附分子 （CAMs）由胎儿胰腺细胞表达，并了解其 在细胞-细胞粘附、增殖和内分泌中的功能作用 分化 特别是，我们已经确定EpCAM是一个主要的 胰腺上皮细胞-细胞粘附介质。 有趣的是， 该CAM似乎参与上皮细胞生长。 的一部分 这项工作需要使用共聚焦显微镜和IVEM在 NCMR。 这些数据是一份正在准备中的手稿的主题（1）。 此外，根据我们以往的经验， 间充质源性生长因子如HGF/SF在 增殖的人胎儿胰腺细胞，我们已经检查了 HGF/SF的C-MET受体在人类中的表达模式 在胎儿和成人的胰腺中。 这些实验 确定C-MET仅限于上皮隔室， 发育中的人类胰腺， 在成人内分泌细胞（胰岛）上表达 胰腺（2）。 最后，我们寻找内分泌标志物 分化导致GAD 65（谷氨酸）的鉴定 脱羧酶，65 kD）进入上皮细胞的途径， 内分泌分化（即胰岛素和/或胰高血糖素表达）。 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).