Reactive oxygen species (ROS) serve both as pathological mediators and as physiological signaling mediators (see Theopold). Owusu-Ansah and Banerjee show that at the time when hematopoietic progenitor cells are becoming quiescent and beginning to differentiate in the medullary region of the fly lymph gland ROS increases. In contrast, the fully differentiated progeny cells in the adjacent cortical zone of the lymph gland lack high concentrations of ROS, as do cells before the onset of differentiation in the medullary region. Introduction of ROS scavenging proteins inhibited differentiation of the progenitor cells, whereas genetic disruptions that increase ROS resulted in the appearance of progenitors in the medullary region at the expense of progenitor cells (an indication of premature differentiation). Conditions that increased ROS also activated a reporter of Jun N-terminal kinase (JNK) signaling, and the premature differentiation in response to increased ROS was prevented by introduction of a dominant-negative form of the Drosophila homolog of JNK. Conditions that increased ROS stimulated the activity of the transcription factor FoxO, which is activated by JNK signaling, and decreased the activity of the transcriptional repressor Polycomb. Overexpression of FoxO resulted in premature progenitor differentiation into two of the three types of hematopoietic cells. Forced down-regulation of Polycomb activity increased the production of the third type of hematopoietic cell. These data indicate that ROS act through JNK to regulate transcription factor activity, allowing differentiation of the three types of hematopoietic cells in flies.
E. Owusu-Ansah, U. Banerjee, Reactive oxygen species prime Drosophila haematopoietic progenitors for differentiation. Nature 461, 537–541 (2009). [PubMed]
U. Theopold, A bad boy comes good. Nature 461, 486–487 (2009). [PubMed]