The Retinoblastoma pathway regulates stem cell proliferation in freshwater planarians

► Lophotrochozoa have lost an ancestral E2F7/8 homolog in the Retinoblastoma pathway. ► Flatworms have additionally lost activating-E2F(1-3) and CyclinE homologs. ► The planarian homologs to Rb, E2F4/5, and Dp are primarily expressed in stem cells. ► Retinoblastoma is required for adult stem cell self-renewal (and regeneration). ► Retinoblastoma is required either directly or indirectly for cell survival.