A Non-Cell Autonomous Dermal Hedgehog Signaling Mechanism for Follicular Neoplasia and Induction
April 2023
in “
Journal of Investigative Dermatology
”
SHH signaling pathway Gorlin syndrome epidermal tumors follicular tumors Twist2-CreERT2 R26-tdTO dermal sheath Smo expression follicular neoplasms hair morphogenesis Wnt-mediated mechanism scarring alopecia Sonic Hedgehog signaling pathway skin tumors hair tumors Twist2-CreERT2 model R26-tdTO model hair growth Wnt signaling scarring hair loss
TLDR Mutations in the SHH pathway in certain skin cells can cause skin tumors and abnormal hair growth.
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.
