PMID- 12632175 OWN - NLM STAT- MEDLINE DCOM- 20030916 LR - 20190613 IS - 0949-944X (Print) IS - 0949-944X (Linking) VI - 213 IP - 2 DP - 2003 Mar TI - Snail is required for Delta endocytosis and Notch-dependent activation of single-minded expression. PG - 65-72 AB - In the Drosophila embryo, the mesectoderm corresponds to a single row of cells abutting the mesoderm. It is specified by the expression of the single-minded (sim) gene. The information that precisely positions the sim-expressing cells along the dorso-ventral axis is incompletely understood. Previous studies have shown that Dorsal and Twist activate sim expression in a large ventral domain, while two negative regulators, Snail (Sna) and Suppressor of Hairless [Su(H)], repress sim expression in the mesoderm and neuroectoderm, respectively. Repression by Su(H) is relieved in the presumptive mesectoderm by Notch signaling. In this paper, we show that Sna also has a positive regulatory function on sim expression in the presumptive mesectoderm. This positive effect of Sna depends on the Su(H)-binding sites within the sim promoter, suggesting that Sna regulates Notch signaling. In addition, we find that Delta is endocytosed together with the extracellular domain of Notch. The endocytosis of Delta is only seen in the mesoderm and requires the activity of the sna and neuralized (neur) genes. Interestingly, the Neur-mediated endocytosis of Delta has recently been shown to be sufficient for the non-autonomous activation of Notch target genes in wing imaginal discs. We therefore propose a novel model in which Sna positions the mesectoderm via its dual regulatory activity. In this model, Sna cell-autonomously represses sim expression in the mesoderm and relieves Su(H)-dependent repression in a cell non-autonomous fashion by promoting the Neur-dependent endocytosis of Delta in the mesoderm. FAU - Morel, Veronique AU - Morel V AD - Ecole Normale Superieure, CNRS UMR 8542, 46 rue d'Ulm, 75230 Paris Cedex 05, France. FAU - Le Borgne, Roland AU - Le Borgne R FAU - Schweisguth, Francois AU - Schweisguth F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20030205 PL - Germany TA - Dev Genes Evol JT - Development genes and evolution JID - 9613264 RN - 0 (Basic Helix-Loop-Helix Transcription Factors) RN - 0 (DNA-Binding Proteins) RN - 0 (Drosophila Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Membrane Proteins) RN - 0 (N protein, Drosophila) RN - 0 (Nuclear Proteins) RN - 0 (Receptors, Notch) RN - 0 (Snail Family Transcription Factors) RN - 0 (Transcription Factors) RN - 0 (delta protein) RN - 0 (sim protein, Drosophila) RN - 0 (sna protein, Drosophila) SB - IM MH - Animals MH - Basic Helix-Loop-Helix Transcription Factors MH - DNA-Binding Proteins/*biosynthesis/genetics/*physiology MH - Drosophila/*embryology/genetics/physiology MH - Drosophila Proteins/physiology MH - Embryo, Nonmammalian MH - Endocytosis MH - *Gene Expression Regulation, Developmental MH - Intracellular Signaling Peptides and Proteins MH - Membrane Proteins/*physiology MH - Nuclear Proteins/*biosynthesis/genetics MH - Receptors, Notch MH - Snail Family Transcription Factors MH - Transcription Factors/*physiology EDAT- 2003/03/13 04:00 MHDA- 2003/09/17 05:00 CRDT- 2003/03/13 04:00 PHST- 2002/10/30 00:00 [received] PHST- 2002/12/10 00:00 [accepted] PHST- 2003/03/13 04:00 [pubmed] PHST- 2003/09/17 05:00 [medline] PHST- 2003/03/13 04:00 [entrez] AID - 10.1007/s00427-003-0296-x [doi] PST - ppublish SO - Dev Genes Evol. 2003 Mar;213(2):65-72. doi: 10.1007/s00427-003-0296-x. Epub 2003 Feb 5.