The PDGF/VEGF receptor controls blood cell survival in Drosophila.
The Drosophila PDGF/VEGF receptor (PVR) has known functions in the guidance of cell migration. We now demonstrate that during embryonic hematopoiesis, PVR has a role in the control of antiapoptotic cell survival. In Pvr mutants, a large fraction of the embryonic hemocyte population undergoes apoptosis, and the remaining blood cells cannibalistically phagocytose their dying peers. Consequently, total hemocyte numbers drop dramatically during embryogenesis, and large aggregates of engorged macrophages carrying multiple apoptotic corpses form. Hemocyte-specific expression of the pan-caspase inhibitor p35 in Pvr mutants eliminates hemocyte aggregates and restores blood cell counts and morphology. Additional rescue experiments suggest involvement of the Ras pathway in PVR-mediated blood cell survival. In cell culture, we demonstrate that PVR directly controls survival of a hemocyte cell line. This function of PVR shows striking conservation with mammalian hematopoiesis and establishes Drosophila as a model to study hematopoietic cell survival in development and disease.
Brückner
Katja
K
Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. kbrueckn@genetics.med.harvard.edu
Kockel
Lutz
L
Duchek
Peter
P
Luque
Carlos M
CM
Rørth
Pernille
P
Perrimon
Norbert
N
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001773:Blood Cells / Q000166:cytology / Q000378:metabolism*; D002449:Cell Aggregation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics*; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006410:Hematopoiesis / Q000235:genetics*; D008264:Macrophages / Q000502:physiology; D023421:Models, Animal; D009154:Mutation / Q000235:genetics; D010587:Phagocytosis / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D014764:Viral Proteins; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D029721:Drosophila Proteins; D011506:Proteins; D014764:Viral Proteins; C492234:p35 protein, Baculovirus; C438368:Pvr protein, Drosophila; D020794:Receptor Protein-Tyrosine Kinases; D018631:ras Proteins