RESUMEN
A programmed developmental switch to G / S endocycles results in tissue growth through an increase in cell size. Unscheduled, induced endocycling cells (iECs) promote wound healing but also contribute to cancer. Much remains unknown, however, about how these iECs affect tissue growth. Using the D. melanogaster wing disc as model, we find that populations of iECs initially increase in size but then subsequently undergo a heterogenous arrest that causes severe tissue undergrowth. iECs acquired DNA damage and activated a Jun N-terminal kinase (JNK) pathway, but, unlike other stressed cells, were apoptosis-resistant and not eliminated from the epithelium. Instead, iECs entered a JNK-dependent and reversible senescent-like arrest. Senescent iECs promoted division of diploid neighbors, but this compensatory proliferation did not rescue tissue growth. Our study has uncovered unique attributes of iECs and their effects on tissue growth that have important implications for understanding their roles in wound healing and cancer.
Asunto(s)
Daño del ADN , Drosophila melanogaster , Alas de Animales , Animales , Alas de Animales/crecimiento & desarrollo , Alas de Animales/metabolismo , Drosophila melanogaster/crecimiento & desarrollo , Drosophila melanogaster/genética , Proliferación Celular , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Apoptosis , Discos Imaginales/crecimiento & desarrollo , Discos Imaginales/metabolismo , Cicatrización de Heridas/genética , Senescencia Celular , Sistema de Señalización de MAP Quinasas , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/genética , Ciclo CelularRESUMEN
A programmed developmental switch to G / S endocycles results in tissue growth through an increase in cell size. Unscheduled, induced endocycling cells (iECs) promote wound healing but also contribute to cancer. Much remains unknown, however, about how these iECs affect tissue growth. Using the D. melanogasterwing disc as model, we find that populations of iECs initially increase in size but then subsequently undergo a heterogenous arrest that causes severe tissue undergrowth. iECs acquired DNA damage and activated a Jun N-terminal kinase (JNK) pathway, but, unlike other stressed cells, were apoptosis-resistant and not eliminated from the epithelium. Instead, iECs entered a JNK-dependent and reversible senescent-like arrest. Senescent iECs promoted division of diploid neighbors, but this compensatory proliferation did not rescue tissue growth. Our study has uncovered unique attributes of iECs and their effects on tissue growth that have important implications for understanding their roles in wound healing and cancer.