In Drosophila, neuronal precursor cell determination is regulated by basic Helix-Loop-Helix (bHLH) transcription factors. These include proneural bHLH activator proteins such as Achaete, Scute and Lethal of Scute. A lateral inhibition process mediated by the Notch signaling pathway inhibits proneural gene expression. Notch signaling is known to result in transcriptional repression of proneural genes. The goals of this project are to study the post-transcriptional regulation of the Drosophila proneural genes Achaete, Scute, and Lethal of Scute. The investigator provides evidence that activation of the Notch pathway also results in post-translational inhibition of the Achaete proneural protein through its C-terminal transcriptional activation (TA) domain. An N terminal domain also strongly inhibits Achaete TA activity. Homologous C- and N-terminal domains are highly conserved in the Scute and Lethal of Scute (L'Sc) proteins, which may be post-transcriptionally regulated by the same pathways.