Heixuedian (heix), a potential melanotic tumor suppressor gene, exhibits specific spatial and temporal expression...

The Drosophila heixuedian (heix) is the ortholog of human UBIAD1 gene (a.k.a TERE1). The protein product of UBIAD1/heix has multiple enzymatic activities, including the vitamin K2 and the non-mitochondrial CoQ10 biosynthesis. However, the expression pattern of UBIAD1/Heix during metazoan development has not been systematically studied. In this paper, we found that loss of function of heix resulted in pathological changes of larval hematopoietic system, including lymph gland hypertrophy, hemocyte overproliferation and aberrant differentiation, and melanin mass formation. Overexpression of heix cDNA under the tubulin Gal4 driver rescued the above hematopoietic defects. Interestingly, Heix was specifically expressed in plasmatocyte/macrophage lineage in srp driven EGFP positive cells on the head mesoderm during embryogenesis, while it was highly expressed in crystal cells in the primary lobes of the third instar larval lymph gland. Using qRT-PCR analysis, loss of function of heix caused aberrant activation of multiple hemocyte proliferation-related as well as immune-related pathways, including JAK/STAT pathway, Ras/MAPK pathway, IMD pathway and Toll pathway. These data suggested that heix is a potential melanotic tumor suppressor gene and plays a pivotal role in both hemocytes proliferation and differentiation in Drosophila.