Find in Library

Basal cell carcinoma (BCC) originate from Hedgehog/Patched signaling-activated epidermal stem cells. However, the chemically induced tumorigenesis of mice with a <i>CD4Cre</i>-mediated biallelic loss of the Hedgehog signaling repressor Patched also induces BCC formation. Here, we identified the cellular origin of <i>CD4Cre</i>-targeted BCC progenitors as rare Keratin 5⁺ epidermal cells and show that wildtype <i>Patched</i> offspring of these cells spread over the hair follicle/skin complex with increasing mouse age. Intriguingly, <i>Patched</i> mutant counterparts are undetectable in age-matched untreated skin but are getting traceable upon applying the chemical tumorigenesis protocol. Together, our data show that biallelic <i>Patched</i> depletion in rare Keratin 5⁺ epidermal cells is not sufficient to drive BCC development, because the spread of these cells is physiologically suppressed. However, bypassing the repression of <i>Patched</i> mutant cells, e.g., by exogenous stimuli, leads to an accumulation of BCC precursor cells and, finally, to tumor development.