A Non-Cell Autonomous Dermal Hedgehog Signaling Mechanism for Follicular Neoplasia and Induction

The study, conducted by researchers at Northwestern University Feinberg School of Medicine and The University of Texas Southwestern Medical Center, investigates the role of SHH (Sonic Hedgehog) signaling pathway mutations in Gorlin syndrome, a hereditary condition characterized by the development of numerous epidermal and follicular tumors. The researchers used a Twist2-CreERT2;R26-tdTO lineage tracing model to identify Twist2-expressing cells in the dermis and dermal sheath of mouse skin. They found that constitutively active Smo expression in these dermal cells led to the formation of numerous follicular neoplasms and abnormal hair morphogenesis. The study also observed follicular induction in traditionally non-hair bearing skin, suggesting a Wnt-mediated mechanism. The findings suggest that Gorlin syndrome phenotypes may not be solely mediated by epidermal dysregulation, highlighting the importance of the tumor and dermal microenvironment in regulating epidermal growth and development. This has significant clinical implications for hair regrowth in cases of scarring alopecia.