title: Dorsal-ventral pattern of Delta trafficking is established by a Snail-Tom-Neuralized pathway.
abstract: The intracellular trafficking of the Notch ligand Delta plays an important role in the activation of the Notch pathway. We have addressed the snail-dependent regulation of Delta trafficking during the plasma membrane growth of the mesoderm in the Drosophila embryo. We show that Delta is retained in endocytic vesicles in the mesoderm but expressed on the surface of the adjacent ectoderm. This trafficking pattern requires Neuralized. We developed a protocol based on chromosomal deletion and microarray analysis that led to the identification of tom as the target of snail regulating Delta trafficking. Snail represses Tom expression in the mesoderm and thereby activates Delta trafficking. Overexpression of Tom abolishes Delta trafficking and signaling to the adjacent mesoectoderm. Loss of Tom produces mesoderm-type Delta trafficking in the entire blastoderm epithelium and an expansion of mesoectoderm gene expression. We propose that Tom antagonizes the activity of Neuralized and thus establishes a sharp mesoderm-mesoectoderm boundary of Notch signaling.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Stefano
authors.initials: S
authors.lastname: De Renzis
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.forename: R
authors.initials: R
authors.lastname: Zinzen
authors.forename: Eric
authors.initials: E
authors.lastname: Wieschaus
mesh_terms: D000818:Animals; D019521:Body Patterning; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D017344:Genes, Insect; D008297:Male; D008648:Mesoderm / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D015053:Zygote / Q000378:metabolism
chemical_list: C109219:Brd protein, Drosophila; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D000071250:Snail Family Transcription Factors; C405938:Tom protein, Drosophila; D014157:Transcription Factors; C062236:dl protein, Drosophila; C000604451:sna protein, Drosophila; D044767:Ubiquitin-Protein Ligases; C071006:neur protein, Drosophila