Endocytosis regulates the growth and development of hematopoietic cells in Drosophila melanogaster

Hematopoiesis is a process by which undifferentiated stem cells give rise to specialized blood cells through specific signals received from a stem cell niche. The lymph gland of Drosophila melanogaster has three compartments: Cortical Zone (CZ), Medulary Zone (MZ), and a Posterior Signaling Center (PSC). These compartments function together to derive all blood cells in the fruit fly from progenitor stem cells. The Posterior Signaling Center acts as the stem cell niche, which controls the growth and development of the progenitor cells into differentiated cells. Our goal was to investigate if endocytosis affects Hematopoiesis by over expressing and down regulating components of the endosomal fusion machinery. Manipulation of endocytic fusion proteins in differentiating hemocytes causes loss of MZ progenitors. This suggests a role for secreted signals originating from the CZ that maintain the progenitor population. We identified a differential role for lysosomes in the PSC and MZ, where they are active, versus the CZ where its activity is reduced. Interestingly, the expression of the transmembrane domain along with its cytoplasmic tail of human Lamp1 in both the PSC and MZ leads to a loss of progenitor cells and a fully differentiated lymph gland. This suggests a novel role for lysosomal function in maintenance signaling between niche and progenitor cells. In addition, Rabex5 and Gilgamesh appear to regulate the proliferation of MZ progenitors. This study demonstrates novel roles for the endocytic machinery in hematopoiesis.