1322 A non-cell autonomous dermal hedgehog signaling mechanism for follicular neoplasia and induction

Gorlin syndrome (also known as basal cell nevus syndrome) is a hereditary condition characterized by development of numerous epidermal and follicular tumors. Mutations in theSHH signaling pathway are key drivers this disease. It currently unknown whether SHH mutations non-epidermal types play role phenotypes, the tumor microenvironment, or altered skin development. Through lineage tracing using tamoxifen inducible Cre-recombinase under control Twist2 promoter (Twist2-CreERT2;R26-tdTO), we identify Twist2-expressing cells mouse located dermis dermal sheath. Using Twist2-CreERT2; R26-Smo, demonstrate that constitutively active Smo expression results formation neoplasms abnormal hair morphogenesis. Additionally, find induction traditionally non-hair bearing such plantar foot pad, suggesting downstream Wntmediated mechanism. Our preliminary data provides evidence phenotypes may not be mediated purely dysregulation. non-cell autonomous mechanism neoplasia reveal importance microenvironment regulating growth demonstrating non-hair-bearing has important clinical implications regrowth for scarring alopecia.