Abstract
The hematopoietic system of Drosophila is a powerful genetic model for studying hematopoiesis, and vesicle trafficking is important for signal transduction during various developmental processes; however, its interaction with hematopoiesis is currently largely unknown. In this article, we selected three endosome markers, Rab5, Rab7, and Rab11, that play a key role in membrane trafficking and determined whether they participate in hematopoiesis. Inhibiting Rab5 or Rab11 in hemocytes or the cortical zone (CZ) significantly induced cell overproliferation and lamellocyte formation in circulating hemocytes and lymph glands and disrupted blood cell progenitor maintenance. Lamellocyte formation involves the JNK, Toll, and Ras/EGFR signaling pathways. Notably, lamellocyte formation was also associated with JNK-dependent autophagy. In conclusion, we identified Rab5 and Rab11 as novel regulators of hematopoiesis, and our results advance the understanding of the mechanisms underlying the maintenance of hematopoietic homeostasis as well as the pathology of blood disorders such as leukemia.
Highlights
Drosophila is a powerful genetic model for studying hematopoiesis due to the conservation between its hematopoietic system and that of mammals, including conserved regulatory factors and signaling pathways (Yu et al, 2018a; Banerjee et al, 2019)
Given that Rab5 and Rab11 can affect the numbers of circulating hemocytes, we sought to determine whether they control homeostasis of the lymph gland or circulating hemocytes
Vesicle trafficking is a critical component of signal transduction in multiple developmental processes, and aberrant membrane transport significantly alters the signal output
Summary
Drosophila is a powerful genetic model for studying hematopoiesis due to the conservation between its hematopoietic system and that of mammals, including conserved regulatory factors and signaling pathways (Yu et al, 2018a; Banerjee et al, 2019) By utilizing this model, we can improve the understanding of the molecular mechanisms underlying some blood system diseases, such as leukemia. Three distinct zones are identified within the anterior lobe: the medullary zone (MZ), where prohemocytes (blood cell progenitors) reside; a cortical zone (CZ) consisting of mature hemocytes, including plasmatocytes and crystal cells; and a posterior signaling center (PSC), which controls lymph gland homeostasis under both normal conditions and immune challenge (Jung et al, 2005; Yu et al, 2018a). The lymph gland can produce another type of hemocyte, the lamellocyte, which is much
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