TY - JOUR
T1 - The Scabrous protein can act as an extracellular antagonist of Notch signaling in the Drosophila wing
AU - Lee, E. Chiang
AU - Yu, Sung Yun
AU - Baker, Nicholas E.
N1 - Funding Information:
We thank Y. Li for help with unpublished experiments; R. Fleming, L. Seugnet, F.M. Hoffman, F. Schweisguth, D. Doherty, S. Artavanis-Tsakonas, E. Knust, M. Mlodzik, E. Giniger, M. Haenlin, S. Carroll for fly stocks; R. Fleming, D. Stein and S. Artavanis for DNA; S. Artavanis, R. Nusse for antibodies; and R. Cagan, P. Stanley and C. Wesley for discussing unpublished data. Antibodies against Cut (mAb 2B10, developed by G. Rubin) and against β-galactosidase (mAb 40-1a, developed by J.R. Sanes) were obtained from the Developmental Studies Hybridoma Bank (Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, and Department of Biological Sciences, University of Iowa). The manuscript was improved by comments from C. Delidakis and D. Stein. Supported by grants from the American Heart Association (New York City affiliate) and the American Cancer Society.
PY - 2000/8/1
Y1 - 2000/8/1
N2 - Notch (N) is a receptor for signals that inhibit neural precursor specification [1-6]. As N and its ligand Delta (Dl) are expressed homogeneously, other molecules may be differentially expressed or active to permit neural precursor cells to arise intermingled with non-neural cells [7,8]. During Drosophila wing development, the glycosyltransferase encoded by the gene fringe (fng) promotes N signaling in response to Dl, but inhibits N signaling in response to Serrate (Ser), which encodes a ligand that is structurally similar to Dl. 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 Dl 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 Dl and Ser, and can act as an antagonist of N signaling.
AB - Notch (N) is a receptor for signals that inhibit neural precursor specification [1-6]. As N and its ligand Delta (Dl) are expressed homogeneously, other molecules may be differentially expressed or active to permit neural precursor cells to arise intermingled with non-neural cells [7,8]. During Drosophila wing development, the glycosyltransferase encoded by the gene fringe (fng) promotes N signaling in response to Dl, but inhibits N signaling in response to Serrate (Ser), which encodes a ligand that is structurally similar to Dl. 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 Dl 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 Dl and Ser, and can act as an antagonist of N signaling.
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U2 - 10.1016/S0960-9822(00)00622-9
DO - 10.1016/S0960-9822(00)00622-9
M3 - Article
C2 - 10959842
AN - SCOPUS:0343878228
SN - 0960-9822
VL - 10
SP - 931
EP - 934
JO - Current Biology
JF - Current Biology
IS - 15
ER -