The expression of the Drosophila awd gene during normal development and in neoplastic brain tumors caused by lgl mutations.
The abnormal wing discs (awd) gene of Drosophila is homologous to the nm23 gene of mammals, a gene whose expression is altered in metastatic tumors. Both awd and nm23 encode nucleoside diphosphate kinases (NDP kinases). We have examined the accumulation of AWD/NDP kinase during normal development by assaying enzyme activity in extracts. There is a nearly constant level of activity throughout larval and pupal development. We have examined the tissue-specific transcription of the awd gene by RNA in situ hybridization and by reporter gene expression. In imaginal discs and brains there is no detectable awd gene expression until the beginning of the third larval instar, despite the constant level of enzyme activity measured in extracts of larvae and pupae. The most intense awd gene expression in imaginal discs and brains occurs after the end of larval development. We have also examined awd gene expression in neoplastic brain tumors caused by mutations in the lethal giant larvae (lgl) gene. In lgl mutant brains, as in normal brains, awd gene expression begins during the third larval instar. No tumors form in brains from lgl-; awd- double mutant larva, so awd gene expression is required for tumor formation and/or proliferation. There is more accumulation of AWD/NDP kinase in lgl- mutant brains than there is in normal brains. Using an awd reporter gene, we show that this is a consequence of an increased proportion of awd gene-expressing cells in mutant brains. Using the same awd reporter gene as a marker of donor cells, we have confirmed the invasiveness of lgl-induced neuroblastomas.
Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218.
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L
Timmons
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Hersperger
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E
Woodhouse
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J
Xu
L Z
LZ
Liu
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A
Shearn
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins; D015870:Gene Expression; D007301:Insect Hormones / Q000235:genetics* / Q000378:metabolism; D007763:Lac Operon; D009154:Mutation; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D029721:Drosophila Proteins; D007301:Insect Hormones; D009701:Nucleoside-Diphosphate Kinase; C061642:awd protein, Drosophila