Understanding molecular mechanisms underlying the formation of the blue nevus and

正常皮肤的发育依赖于多种细胞类型的精细相互作用 由外胚层、神经外胚层和中胚层组成。痣和其他错构瘤可能发生在 异常的细胞相互作用导致细胞在不适当的位置沉积。重要的因素 角质形成细胞、黑素细胞、成纤维细胞和其他细胞类型之间的通讯可能协调了 成人体内的细胞定位和重新激活可能会导致癌症和转移。确定分子 负责诱导良性错构瘤，如蓝痣，是阐明其机制的第一步。 肿瘤的形成和发展。 在这里，我们将使用免疫缺陷小鼠移植系统中的皮肤重建模型来开始 破译导致蓝痣形成的诱导性和抑制性信号。1996年，普鲁蒂和 同事们发现，当他们将特定类型的成纤维细胞系与新生儿表皮细胞相结合时 并将这种混合物移植到免疫缺陷小鼠身上，移植区域出现了常见的蓝痣(CBN)。 或Jadassohn(NSJ)皮脂痣(NSJ)取决于使用的细胞。表皮细胞移植 单独使用只会导致疤痕，而将表皮细胞和新鲜的完整真皮结合在一起可以正常再生。 皮肤表面有毛囊、黑素细胞和皮脂腺。 在这项研究中，我们将使用基因表达微阵列来比较诱导蓝色的间充质细胞系 与那些不这样做的人在一起。我们计划确定对迁徙、生存和生存至关重要的候选基因 黑素细胞的定位。这些候选基因将在非诱导性成纤维细胞中稳定过表达。 细胞，以测试蓝色痣表型的诱导。最终，我们将评估蓝雀斑和其他 人类的黑色素细胞错构瘤表达已确定的基因。 这些研究的结果将为K奖或新的研究人员RO1博士奠定基础。 卡斯特罗-索西奥，首席调查员。

The development of normal skin depends upon the elaborate interaction of numerous cell types derived from ectoderm, neuroectoderm and mesoderm. Nevi and other hamartomas presumably develop when aberrant cellular interactions lead to deposition of cells in inappropriate locations. Factors important for communication between keratinocytes, melanocytes, fibroblasts and other cell types likely orchestrate proper cell positioning and their reactivation in the adult may lead to cancer and metastasis. Determining molecules responsible for induction of benign hamartomas, like blue nevi, is a first step in elucidating the mechanisms of tumor formation and progression. Here we will use a skin reconstitution model in an immunodeficient mouse grafting system to begin to decipher the inductive and inhibitory signals that lead to the formation of a blue nevus. In 1996, Prouty and coworkers found that when they combined specific types of fibroblast cell lines with neonatal epidermal cells and grafted the mixture onto immunodeficient mice, the grafted area developed a common blue nevus (CBN) or a nevus sebaceus of Jadassohn (NSJ) depending on which cells were used. Grafting of epidermal cells alone resulted only in a scar, while combining epidermal cells with fresh whole dermis regenerated normal appearing skin possessing hair follicles, melanocytes and sebaceous glands. In this study we will use gene expression microarrays to compare mesenchymal cell lines that induce blue nevi with those that do not. We plan to identify candidate genes important for the migration, survival and localization of melanocytes. These candidate genes will be stably overexpressed in non-inductive fibroblast cells to test for induction of a blue nevus phenotype. Ultimately, we will evaluate whether blue nevi and other melanocytic hamartomas from humans express the identified genes. The results from these studies will form the foundation for a K-award or new investigator RO1 for Dr. Castelo-Soccio, the principal investigator.