Direct sensing of systemic and nutritional signals by hematopoietic progenitors in Drosophila

The Drosophila lymph gland is a hematopoietic organ in which progenitor cells, which are most akin to the common myeloid progenitor or CMP in mammals, proliferate and differentiate into three types of mature cells – plasmatocytes, crystal cells and lamellocytes – the functions of which are reminiscent of mammalian myeloid cells(1). During the first and early second instars of larval development, the lymph gland contains only progenitors, whereas in the third instar, a medial region of the primary lobe of the lymph gland called the medullary zone (MZ) contains these progenitors(2), while maturing blood cells are found juxtaposed in a peripheral region designated the cortical zone (CZ)(2). A third group of cells referred to as the posterior signaling center (PSC) functions as a hematopoietic niche(3,4). Similar to mammalian myeloid cells, Drosophila blood cells respond to multiple stresses including hypoxia, infection, and oxidative stress(5–7). However, how systemic signals are sensed by myeloid progenitors to regulate cell fate determination has not been well described. Here, we show that the hematopoietic progenitors of Drosophila are direct targets of systemic (insulin) and nutritional (essential amino acid) signals, and that these systemic signals maintain the progenitors by promoting Wingless (WNT in mammals) signaling. We expect that this study will promote investigation of such possible direct signal sensing mechanisms by mammalian myeloid progenitors.