EGFR and cyst: Although ROS derived from the germline has been shown to activate EGFR in cyst cells33, it is likely that EGFR activation is induced via multiple mechanisms and not simply through the upregulation of germline Spitz. Importantly, previous findings have shown that the overexpression of secreted Spitz is not sufficient to robustly activate EGFR18 and suggested that EGFR levels may also need to be increased.