Stem Cell Regulation by the NF2 Tumor Suppressor Merlin

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DESCRIPTION (provided by applicant): Stem cells are maintained within the adult body in microenvironments that regulate both the differentiation and proliferation of these cells. The role that stem cells have in cancer development is poorly understood but critically important in normal and cancer biology. Our preliminary observations indicate that in vivo ablation of the Nf2 tumor suppressor, Merlin in the skin alters normal epidermal development. Therefore we hypothesize that Merlin is required for normal regulation of epithelial stem cells. Our long term objectives are: 1)To determine the role of Merlin in regulation of the epidermal stem cell compartment. 2)To determine whether Merlin organizes membrane receptor signaling in the epidermal stem cell niche. 3)To determine whether Nf2 deficiency promotes epidermal tumorigenesis. We have generated mice specifically deleting the Nf2 gene from mouse skin. We will utilize these mice in addition to molecular approaches to investigate the role of Merlin in the stem cell compartment. These studies will contribute to our understanding of how the Nf2 tumor suppressor regulates cell-cell interactions specifically between stem cells and the surrounding niche and the role these interactions have in tumor development and progression into metastatic cancer.