The Scabrous protein can act as an extracellular antagonist of Notch signaling in the Drosophila wing

Notch (N) is a receptor for signals that inhibit neural precursor specifica tion [1-6], As N and its ligand Delta (DI) are expressed homogeneously, oth er molecules may be differentially expressed or active to permit neural pre cursor cells to arise intermingled with nonneural cells [7,8], During Droso phila wing development, the glycosyltransferase encoded by the gene fringe (fng) promotes N signaling In response to DI, but inhibits N signaling in r esponse to Serrate (Ser), which encodes a ligand that is structurally simil ar to DI, Dorsal expression of Fng protein localizes N signaling to the dor soventral (DV) wing margin [9-11], The secreted protein Scabrous (Sca) is a candidate for modulation of N in neural cells. Mutations at the scabrous ( sca) locus alter the locations where precursor cells form in the peripheral nervous system [12,13]. Unlike fringe, sea mutations act cell non-autonomo usly [12]. Here, we report that targeted misexpression of Sea during wing d evelopment inhibited N signaling, blocking expression of all N target genes . Sea reduced N activation in response to DI more than in response to Ser, Ligand-independent signaling by overexpression of N protein, or by expressi on of activated truncated N molecules, was not inhibited by Sea. Our result s indicate that Sea can act on N to reduce its availability for paracrine a nd autocrine interactions with DI and Ser, and can act as an antagonist of N signaling, (C) 2000 Elsevier Science Ltd. All rights reserved.