Atg2 controls Drosophila hematopoiesis through the PVR/TOR signaling pathways.

The hematopoietic system of Drosophila is a well-established genetic model for studying hematopoiesis mechanisms, which are strictly regulated by multiple signaling pathways. Autophagy-related 2 (Atg2) protein is involved in autophagosome formation through its lipid transfer function; however, other functions in animal development, especially the role of Atg2 in maintaining hematopoietic homeostasis, are unclear. Here, we show that Atg2 knockdown in the cortical zone (CZ) induced the proliferation and differentiation of mature plasmatocytes and disrupted progenitor maintenance in the medullary zone (MZ). We also observed the differentiation of lamellocytes among circulating hemocytes and in the lymph gland, which is rarely observed in healthy larvae. The above results on hematopoiesis disorders are due to Atg2 regulating the Drosophila PDGF/VEGF receptor (PVR) and target of rapamycin (TOR) in the CZ of lymph gland. In conclusion, we identified Atg2 as a previously undescribed regulator of hematopoiesis. Understanding the mechanism of maintenance of hematopoietic homeostasis in Drosophila will help us better evaluate human blood disorder-related diseases.