The Enhancer of split Complex of Drosophila includes four Notch-regulated members of the Bearded gene family

During Drosophila development, transcriptional activation of genes of the E nhancer of split Complex (E(spl)-C) is a major response to cell-cell signal ing via the Notch (N) receptor, Although the structure and function of the E(spl)-C have been studied intensively during the past decade, these effort s have focused heavily on seven transcription units that encode basic helix -loop-helix (bHLH) repressors; the non-bHLH members of the complex have rec eived comparatively little attention, In this report, we analyze the struct ure, regulation and activity of the m1, m2 and md genes of the E(spl)-C, We find that E(spl)m2 and E(spl)m6 encode divergent members of the Bearded (B rd) family of proteins, bringing to four (m alpha, m2, m4 and m6) the numbe r of Brd family genes in the E(spl)-C, We demonstrate that the expression o f both m2 and m6 is responsive to N receptor activity and that both genes a re apparently direct targets of regulation by the N-activated transcription factor Suppressor of Hairless, Consistent with this, both are expressed sp ecifically in multiple settings where N signaling takes place, Particularly noteworthy is our finding that m6 transcripts accumulate both in adult mus cle founder cells in the embryo and in a subset of adepithelial (muscle pre cursor) cells associated with the wing imaginal disc. We show that overexpr ession of either m2 or md interferes with N-dependent cell fate decisions i n adult PNS development, Surprisingly, while misexpression of m6 impairs la teral inhibition, overexpression of m2 potentiates it, suggesting functiona l diversification within the Brd protein family, Finally, we present our in itial studies of the structure, expression and regulation of the newest mem ber of the Brd gene family, Ocho, which is located in the recently identifi ed Bearded Complex.