ECTOPIC EXPRESSION OF WILD-TYPE OR A DOMINANT-NEGATIVE MUTANT OF TRANSCRIPTION FACTOR NTF-1 DISRUPTS NORMAL DROSOPHILA DEVELOPMENT

The Drosophila melanogaster tissue-specific transcription factor NTF-1 was originally identified in vitro as a protein that could bind to an d activate transcription from the Dopa decarboxylase (Ddc) gene. A str ucture-function analysis of NTF-1 led to the identification of a discr ete amino-terminal activation domain. Here, we report that an NTF-1 mu tant lacking the activation domain acts as a trans-dominant inhibitor of NTF-1 activation in tissue culture cells by forming inactive hetero dimers with the full-length protein. Ectopically expressing this domin ant-negative protein or the full-length protein in developing Drosophi la embryos leads to dire developmental consequences. Overexpressing th e trans-dominant NTF-1 leads to lethality, while overexpressing full-l ength NTF-1 results in both lethality and morphogenetic defects. Our r esults suggest that both the activity and the regulation of NTF-1 are critical for viability and proper development of the fly.