Two Distinct E3 Ubiquitin Ligases Have Complementary Functions in the Regulation of Delta and Serrate Signaling in <italic>Drosophila</italic>
<p>Signaling by the Notch ligands Delta (Dl) and Serrate (Ser) regulates a wide variety of essential cell-fate decisions during animal development. Two distinct E3 ubiquitin ligases, Neuralized (Neur) and Mind bomb (Mib), have been shown to regulate Dl signaling in <named-content content-ty...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2005-01-01
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| Series: | PLoS Biology |
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| Online Access: | http://dx.doi.org/10.1371/journal.pbio.0030096 |
| _version_ | 1818888171685937152 |
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| author | Le Borgne Roland Remaud Sylvie Hamel Sophie Schweisguth François |
| author_facet | Le Borgne Roland Remaud Sylvie Hamel Sophie Schweisguth François |
| author_sort | Le Borgne Roland |
| collection | DOAJ |
| description | <p>Signaling by the Notch ligands Delta (Dl) and Serrate (Ser) regulates a wide variety of essential cell-fate decisions during animal development. Two distinct E3 ubiquitin ligases, Neuralized (Neur) and Mind bomb (Mib), have been shown to regulate Dl signaling in <named-content content-type="genus-species">Drosophila melanogaster</named-content> and <italic>Danio rerio,</italic> respectively. While the <italic>neur</italic> and <italic>mib</italic> genes are evolutionarily conserved, their respective roles in the context of a single organism have not yet been examined. We show here that the <italic>Drosophila mind bomb (D-mib)</italic> gene regulates a subset of Notch signaling events, including wing margin specification, leg segmentation, and vein determination, that are distinct from those events requiring <italic>neur</italic> activity. <italic>D-mib</italic> also modulates lateral inhibition, a <italic>neur</italic>- and <italic>Dl</italic>-dependent signaling event, suggesting that D-mib regulates Dl signaling. During wing development, expression of <italic>D-mib</italic> in dorsal cells appears to be necessary and sufficient for wing margin specification, indicating that D-mib also regulates Ser signaling. Moreover, the activity of the <italic>D-mib</italic> gene is required for the endocytosis of Ser in wing imaginal disc cells. Finally, ectopic expression of <italic>neur</italic> in <italic>D-mib</italic> mutant larvae rescues the wing <italic>D-mib</italic> phenotype, indicating that Neur can compensate for the lack of <italic>D-mib</italic> activity. We conclude that D-mib and Neur are two structurally distinct proteins that have similar molecular activities but distinct developmental functions in <italic>Drosophila</italic>.</p> |
| first_indexed | 2024-12-19T16:48:53Z |
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| id | doaj.art-930924bce1884106aadea71c675364f6 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-19T16:48:53Z |
| publishDate | 2005-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-930924bce1884106aadea71c675364f62022-12-21T20:13:35ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852005-01-0134e9610.1371/journal.pbio.0030096.20050521Two Distinct E3 Ubiquitin Ligases Have Complementary Functions in the Regulation of Delta and Serrate Signaling in <italic>Drosophila</italic>Le Borgne RolandRemaud SylvieHamel SophieSchweisguth François<p>Signaling by the Notch ligands Delta (Dl) and Serrate (Ser) regulates a wide variety of essential cell-fate decisions during animal development. Two distinct E3 ubiquitin ligases, Neuralized (Neur) and Mind bomb (Mib), have been shown to regulate Dl signaling in <named-content content-type="genus-species">Drosophila melanogaster</named-content> and <italic>Danio rerio,</italic> respectively. While the <italic>neur</italic> and <italic>mib</italic> genes are evolutionarily conserved, their respective roles in the context of a single organism have not yet been examined. We show here that the <italic>Drosophila mind bomb (D-mib)</italic> gene regulates a subset of Notch signaling events, including wing margin specification, leg segmentation, and vein determination, that are distinct from those events requiring <italic>neur</italic> activity. <italic>D-mib</italic> also modulates lateral inhibition, a <italic>neur</italic>- and <italic>Dl</italic>-dependent signaling event, suggesting that D-mib regulates Dl signaling. During wing development, expression of <italic>D-mib</italic> in dorsal cells appears to be necessary and sufficient for wing margin specification, indicating that D-mib also regulates Ser signaling. Moreover, the activity of the <italic>D-mib</italic> gene is required for the endocytosis of Ser in wing imaginal disc cells. Finally, ectopic expression of <italic>neur</italic> in <italic>D-mib</italic> mutant larvae rescues the wing <italic>D-mib</italic> phenotype, indicating that Neur can compensate for the lack of <italic>D-mib</italic> activity. We conclude that D-mib and Neur are two structurally distinct proteins that have similar molecular activities but distinct developmental functions in <italic>Drosophila</italic>.</p>http://dx.doi.org/10.1371/journal.pbio.0030096Cell BiologyDevelopmentGenetics/Genomics/Gene Therapy |
| spellingShingle | Le Borgne Roland Remaud Sylvie Hamel Sophie Schweisguth François Two Distinct E3 Ubiquitin Ligases Have Complementary Functions in the Regulation of Delta and Serrate Signaling in <italic>Drosophila</italic> PLoS Biology Cell Biology Development Genetics/Genomics/Gene Therapy |
| title | Two Distinct E3 Ubiquitin Ligases Have Complementary Functions in the Regulation of Delta and Serrate Signaling in <italic>Drosophila</italic> |
| title_full | Two Distinct E3 Ubiquitin Ligases Have Complementary Functions in the Regulation of Delta and Serrate Signaling in <italic>Drosophila</italic> |
| title_fullStr | Two Distinct E3 Ubiquitin Ligases Have Complementary Functions in the Regulation of Delta and Serrate Signaling in <italic>Drosophila</italic> |
| title_full_unstemmed | Two Distinct E3 Ubiquitin Ligases Have Complementary Functions in the Regulation of Delta and Serrate Signaling in <italic>Drosophila</italic> |
| title_short | Two Distinct E3 Ubiquitin Ligases Have Complementary Functions in the Regulation of Delta and Serrate Signaling in <italic>Drosophila</italic> |
| title_sort | two distinct e3 ubiquitin ligases have complementary functions in the regulation of delta and serrate signaling in italic drosophila italic |
| topic | Cell Biology Development Genetics/Genomics/Gene Therapy |
| url | http://dx.doi.org/10.1371/journal.pbio.0030096 |
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