Genetic modifier screens on Hairless gain-of-function phenotypes reveal genes involved in cell differentiation, cell growth and apoptosis in Drosophila melanogaster.
Overexpression of Hairless (H) causes a remarkable degree of tissue loss and apoptosis during imaginal development. H functions as antagonist in the Notch-signaling pathway in Drosophila, and the link to growth and apoptosis is poorly understood. To further our insight into H-mediated apoptosis, we performed two large-scale screens for modifiers of a small rough eye phenotype caused by H overexpression. Both loss- and gain-of-function screens revealed known and new genetic interactors representing diverse cellular functions. Many of them did not cause eye phenotypes on their own, emphasizing a specific genetic interaction with H. As expected, we also identified components of different signaling pathways supposed to be involved in the regulation of cell growth and cell death. Accordingly, some of them also acted as modifiers of proapoptotic genes, suggesting a more general involvement in the regulation of apoptosis. Overall, these screens highlight the importance of H and the Notch pathway in mediating cell death in response to developmental and environmental cues and emphasize their role in maintaining developmental cellular homeostasis.
Müller
Dominik
D
University of Hohenheim, Institute of Genetics (240), 70599 Stuttgart, Germany.
Kugler
Sabrina J
SJ
Preiss
Anette
A
Maier
Dieter
D
Nagel
Anja C
AC
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D049108:Cell Enlargement; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000502:physiology; D005124:Eye Abnormalities / Q000235:genetics; D005260:Female; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D008297:Male; D011494:Protein Kinases / Q000502:physiology; D018010:Receptors, Invertebrate Peptide / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology
C111891:DIAP1 protein, Drosophila; D029721:Drosophila Proteins; D051034:Inhibitor of Apoptosis Proteins; D018010:Receptors, Invertebrate Peptide; D014157:Transcription Factors; C064196:dpp protein, Drosophila; C076560:H protein, Drosophila; D011494:Protein Kinases; C066532:Egfr protein, Drosophila; D066246:ErbB Receptors; D048031:JNK Mitogen-Activated Protein Kinases