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 specification [1-6]. As N and its ligand Delta (DI) are expressed homogeneously, other molecules may be differentially expressed or active to permit neural precursor cells to arise intermingled with nonneural cells [7,8]. During Drosophila wing development, the glycosyltransferase encoded by the gene fringe (fng) promotes N signaling in response to DI, but inhibits N signaling in response to Serrate (Ser), which encodes a ligand that is structurally similar to DI. Dorsal expression of Fng protein localizes N signaling to the dorsoventral (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, sca mutations act cell non-autonomously [12]. Here, we report that targeted misexpression of Sca during wing development inhibited N signaling, blocking expression of all N target genes. Sca reduced N activation in response to DI more than in response to Ser. Ligand-independent signaling by overexpression of N protein, or by expression of activated truncated N molecules, was not inhibited by Sca. Our results indicate that Sca can act on N to reduce its availability for paracrine and autocrine interactions with DI and Ser, and can act as an antagonist of N signaling.
Lee
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Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Yu
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Baker
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D000818:Animals; D019521:Body Patterning; D004330:Drosophila / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins; D006023:Glycoproteins / Q000378:metabolism*; D019476:Insect Proteins / Q000378:metabolism*; D007814:Larva; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051880:Receptors, Notch; D015398:Signal Transduction; D014921:Wings, Animal / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism
D029721:Drosophila Proteins; D006023:Glycoproteins; D019476:Insect Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; C066579:sca protein, Drosophila