Zoological Studies

Functional Screening of Human Genes by Expression in Drosophila Identifies Enthoprotin/LqfR as a Regulator of Hematopoiesis

Yung-Heng Chang, Wei-Ru Li, and Y. Henry Sun (2012) We expressed 83 human genes, whose expression is cell cycle dependent and changed in hepatoma, in Drosophila as a screen for conserved functions.  We identified that overexpression of human enthoprotin and 2 novel isoforms of its fly homolog, Liquid facet Related (LqfR), induced melanotic mass formation.  We showed that the effect was due to overproliferation of a hemocyte progenitor in the lymph gland, which is the primary hematopoietic organ in the larval stage.  We further showed that LqfR acts in distinct regions in the lymph gland with distinct functions: acting in the medullary zone (MZ) to regulate progenitor proliferation, acting in the posterior signaling center (PSC) to autonomously repress the size of the PSC, and acting in the MZ to nonautonomously regulate the PSC size.  We also found that LqfR caused accumulation of the activated Notch (N) receptor, and its function requires N signaling.  Our results provide a link from endocytic vesicle trafficking to N activation to hematopoiesis, and suggest that these functions are evolutionarily conserved.