VESTIGIAL GENE-EXPRESSION IN DROSOPHILA-MELANOGASTER IS MODULATED BY THE DTMP POOL

The vestigial (vg) gene of Drosophila melanogaster encodes a nuclear p rotein which plays a key role in wing formation but is also involved i n other developmental processes. We have previously shown that depleti on of the dTMP pool by aminopterin, an inhibitor of the enzyme dihydro folate reductase, or by fluorodeoxyuridine, an inhibitor of thymidylat e synthetase, induces nicks in the wings of wild-type flies and a stro ng vg phenotype in vg(BG)/+ flies and also in individuals heterozygous for a deficiency of the vg locus (vg(B)/+). Furthermore, specific alt erations of the vg locus, caused by intronic insertions, are associate d with resistance to these drugs. In this paper, we show that: (1) dep letion of the dTMP pool by aminopterin leads to a decrease in the amou nt of vg transcripts; (2) insertion of the retrotransposon 412 in the vg(BG) mutant, which is resistant to aminopterin, leads to the formati on of a truncated transcript that is prematurely terminated in the lon g terminal repeat of this transposable element; and (3) aminopterin al so affects the level of this truncated transcript. These results indic ate that alterations of the wing by inhibitors of dTMP synthesis are c aused by an effect of these drugs on levels of vg transcripts; the res istance to such agents observed for the vg(BG) Strain is not due to a qualitatively different effect of this drug on the vg transcript but, rather, is related to the expression of a modified Vg protein encoded by a truncated transcript. These results are compatible with a role fo r vestigial in modulating cell proliferation.