An In Vivo Comparative Study of Sonic, Desert, and Indian Hedgehog Reveals That Hedgehog Pathway Activity Regulates Epidermal Stem Cell Homeostasis

The study investigated the role of hedgehog signaling in epidermal stem cell regulation by overexpressing sonic (Shh), desert (Dhh), and Indian (Ihh) hedgehog in mouse skin. While Ihh overexpression showed no significant effects, Dhh and Shh overexpression led to similar skin manifestations, including epidermal progenitor cell hyperplasia and loss of epidermal tissue renewal, indicating deregulation of stem cell activity. The findings suggested that proper regulation of hedgehog activity is crucial for maintaining epidermal stem cells. Additionally, lesions resembling human basal cell carcinoma (BCC) developed in Shh and Dhh transgenic skin, suggesting BCCs can form outside the stem cell population. This highlighted the potential for identifying genes that increase the proliferative potential of epidermal basal cells and regulate stem cell fate.