Odontogenic Keratocysts Arise from Quiescent Epithelial Rests and Are Associated with Deregulated Hedgehog Signaling in Mice and Humans

摘要: Odontogenic keratocysts in humans are aggressive, noninflammatory jaw cysts that may harbor PTCH1 mutations, leading to constitutive activity of the embryonic Hedgehog (Hh) signaling pathway. We show here epithelial expression Hh transcriptional effector Gli2 is sufficient for highly penetrant keratocyst development transgenic mice. Mouse and human expressed similar markers, tooth misalignment, bone remodeling, craniofacial abnormalities. detected target gene cells lining from both species, implicating deregulated their development. Most mouse arose rests Malassez—quiescent, residual remain embedded periodontal ligament surrounding mature teeth. In Gli2-expressing mice, these were stimulated proliferate, stratify, form a differentiated squamous epithelium. The frequent mice supports idea GLI transcription factor mediates pathological responses humans. Moreover, Gli2-mediated reactivation quiescent indicates retain capacity function as progenitor on activation by an appropriate developmental signal.