Cell-cell signalling mediated by the receptor Notch is used widely across the metazoans to determine cell fate and regulate pattern formation. Notch signals via a conserved regulated intramembrane proteolysis. Recent analyses of the cell biology of the Notch receptor have identified several fundamental mechanisms that contribute to regulate Notch signaling activity in space and time.

The Notch protein (N) acts as a transmembrane receptor for intercellular signals controlling cell fate choices in vertebrates and invertebrates. The signal of N activation may be transduced directly from the cell surface into the nucleus by an evolutionarily conserved transcription factor, Suppressor of Hairless [Su(H)], by its regulated nuclear import. Su(H) is shown here to play a direct role in the immediate response of the genome to N signaling in Drosopbila. First, Su(H) mutant embryos derived from mutant germ-line clones exhibited a "neurogenic" phenotype of neural hypertrophy similar to the N phenotype. Second, the lack of N lateral signaling in these Su(H) mutant embryos was associated with a failure to express the m5 and m8 genes from the Enhancer of split Complex [E(spl)-C]. Finally, the Su(H) protein bound to the regulatory sequences of the E(spl)-C m5 and 1218 genes, and these binding sites were required for the activation of the m5 and m8 promoters in the ventral neuroectoderm. The expression of the E(spl)-C m8 gene was found to be similarly regulated by Su(H) during wing imaginal disc development. Thus, the transcriptional activation of these E(spl)-C genes by Su(H) appears to be a direct and relatively general response to the activation of N. However, we also present evidence indicating that N signals in an Sufffj-independent manner during mesectoderm formation.

Much of the genome is transcribed into long noncoding RNAs (ncRNAs). Previous data suggested that bithoraxoid (bxd) ncRNAs of the Drosophila bithorax complex (BX-C) prevent silencing of Ultrabithorax (Ubx) and recruit activating proteins of the trithorax group (trxG) to their maintenance elements (MEs). We found that, surprisingly, Ubx and several bxd ncRNAs are expressed in nonoverlapping patterns in both embryos and imaginal discs, suggesting that transcription of these ncRNAs is associated with repression, not activation, of Ubx. Our data rule out siRNA or miRNA-based mechanisms for repression by bxd ncRNAs. Rather, ncRNA transcription itself, acting in cis, represses Ubx. The Trithorax complex TAC1 binds the Ubx coding region in nuclei expressing Ubx, and the bxd region in nuclei not expressing Ubx. We propose that TAC1 promotes the mosaic pattern of Ubx expression by facilitating transcriptional elongation of bxd ncRNAs, which represses Ubx transcription.