The homeobox gene mirror links EGF signalling to embryonic dorso-ventral axis formation through Notch activation

• Published in: Nature genetics Vol. 24; no. 4; pp. 429 - 433
• Main Authors: Ruohola-Baker, Hannele, Jordan, Katherine C, Clegg, Nigel J, Blasi, Jennifer A, Morimoto, Alyssa M, Sen, Jonaki, Stein, David, McNeill, Helen, Deng, Wu-Min, Tworoger, Michael
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.04.2000
• Subjects: Animals; Biological and medical sciences; Body Patterning - genetics; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Crosses, Genetic; Cysts; decapentaplegic (dpp) gene; Drosophila; Drosophila melanogaster; Drosophila melanogaster - embryology; Drosophila Proteins; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - embryology; Embryo, Nonmammalian - metabolism; Epidermal growth factor; Epidermal Growth Factor - metabolism; Eye Proteins - genetics; Eye Proteins - metabolism; Female; Follicles; fringe (fng) gene; Fringe protein; Fundamental and applied biological sciences. Psychology; Genes, Homeobox - genetics; Genetic aspects; Homeobox genes; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Homeotic genes; In Situ Hybridization; Insect Proteins - metabolism; Insects; Male; Membrane Proteins - metabolism; mirror (mirr) gene; Molecular and cellular biology; Mutation; N-Acetylglucosaminyltransferases; Notch protein; Oogenesis - genetics; Ovum - cytology; Ovum - metabolism; Physiological aspects; pipe (pip) gene; Receptors, Notch; rhomboid (rho) gene; Signal Transduction - genetics; Transcription Factors; Vertebrates; United States; United States > US; Embryonic development; Insecta; Cell cell interaction; Cell differentiation; Dorsoventral axis; Drosophilidae; Oogenesis; Signal transduction; Membrane receptor; Epidermal growth factor; Arthropoda; Homeotic gene; Invertebrata; Drosophila melanogaster; Diptera
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/74294

Recent studies in vertebrates and Drosophila melanogaster have revealed that Fringe-mediated activation of the Notch pathway has a role in patterning cell layers during organogenesis. In these processes, a homeobox-containing transcription factor is responsible for spatially regulating fringe (fng) expression and thus directing activation of the Notch pathway along the fng expression border. Here we show that this may be a general mechanism for patterning epithelial cell layers. At three stages in Drosophila oogenesis, mirror (mirr) and fng have complementary expression patterns in the follicle-cell epithelial layer, and at all three stages loss of mirr enlarges, and ectopic expression of mirr restricts, fng expression, with consequences for follicle-cell patterning. These morphological changes are similar to those caused by Notch mutations. Ectopic expression of mirr in the posterior follicle cells induces a stripe of rhomboid (rho) expression and represses pipe (pip), a gene with a role in the establishment of the dorsal-ventral axis, at a distance. Ectopic Notch activation has a similar long-range effect on pip. Our results suggest that Mirror and Notch induce secretion of diffusible morphogens and we have identified TGF-β (encoded by dpp) as such a molecule in germarium. We also found that mirr expression in dorsal follicle cells is induced by the EGF-receptor (EGFR) pathway and that mirr then represses pip expression in all but the ventral follicle cells, connecting EGFR activation in the dorsal follicle cells to repression of pip in the dorsal and lateral follicle cells. Our results suggest that the differentiation of ventral follicle cells is not a direct consequence of germline signalling, but depends on long-range signals from dorsal follicle cells, and provide a link between early and late events in Drosophila embryonic dorsal-ventral axis formation.