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Two distinct E3 ubiquitin ligases have complementary functions in the regulation of delta and serrate signaling in Drosophila.

Le Borgne R, Remaud S, Hamel S, Schweisguth F - PLoS Biol. (2005)

Bottom Line: During wing development, expression of D-mib 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 D-mib gene is required for the endocytosis of Ser in wing imaginal disc cells.We conclude that D-mib and Neur are two structurally distinct proteins that have similar molecular activities but distinct developmental functions in Drosophila.

View Article: PubMed Central - PubMed

Affiliation: Ecole Normale Supérieure, CNRS UMR 8542, Paris, France.

ABSTRACT
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 Drosophila melanogaster and Danio rerio, respectively. While the neur and mib genes are evolutionarily conserved, their respective roles in the context of a single organism have not yet been examined. We show here that the Drosophila mind bomb (D-mib) gene regulates a subset of Notch signaling events, including wing margin specification, leg segmentation, and vein determination, that are distinct from those events requiring neur activity. D-mib also modulates lateral inhibition, a neur- and Dl-dependent signaling event, suggesting that D-mib regulates Dl signaling. During wing development, expression of D-mib 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 D-mib gene is required for the endocytosis of Ser in wing imaginal disc cells. Finally, ectopic expression of neur in D-mib mutant larvae rescues the wing D-mib phenotype, indicating that Neur can compensate for the lack of D-mib activity. We conclude that D-mib and Neur are two structurally distinct proteins that have similar molecular activities but distinct developmental functions in Drosophila.

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Expression of Neur in Dorsal Cells Is Sufficient to Rescue the D-mib Mutant PhenotypeD-mib2/D-mib3 mutant discs expressing GFP (A) (GFP staining not shown), Ser (B), Ncdc10 (C), or Neur (D) under the control of Ser-GAL4 were stained for Cut (red). Expression of Ser in dorsal cells did not rescue the D-mib2/D-mib3 wing pouch mutant phenotype (compare [B] with [A]), consistent with D-mib being required for Ser signaling. By contrast, expression of Ncdc10, an activated version of N, led to the deregulated growth of the dorsal compartment and the expression of Cut in most dorsal cells (C), indicating that activated N acts downstream of D-mib. Expression of Neur in dorsal cells was sufficient to compensate for the loss of D-mib activity (D).Bar is 40 μm for all panels.
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pbio-0030096-g008: Expression of Neur in Dorsal Cells Is Sufficient to Rescue the D-mib Mutant PhenotypeD-mib2/D-mib3 mutant discs expressing GFP (A) (GFP staining not shown), Ser (B), Ncdc10 (C), or Neur (D) under the control of Ser-GAL4 were stained for Cut (red). Expression of Ser in dorsal cells did not rescue the D-mib2/D-mib3 wing pouch mutant phenotype (compare [B] with [A]), consistent with D-mib being required for Ser signaling. By contrast, expression of Ncdc10, an activated version of N, led to the deregulated growth of the dorsal compartment and the expression of Cut in most dorsal cells (C), indicating that activated N acts downstream of D-mib. Expression of Neur in dorsal cells was sufficient to compensate for the loss of D-mib activity (D).Bar is 40 μm for all panels.

Mentions: The functional assay was then used to genetically position the requirement for the D-mib gene activity relative to Ser and N (Figure 8). Expression of an activated version of N, Ncdc10 [51], led to the activation of Cut and promoted growth in dorsal cells of D-mib2/D-mib3 mutant discs (Figure 8C). This indicates that D-mib acts at a step upstream of N activation. By contrast, elevated levels of Ser expression failed to restore Cut expression and growth of the wing pouch in D-mib2/D-mib3 mutant larvae (Figure 8B). This confirms that Ser signaling requires the activity of the D-mib gene, i.e., that D-mib acts downstream of Ser.


Two distinct E3 ubiquitin ligases have complementary functions in the regulation of delta and serrate signaling in Drosophila.

Le Borgne R, Remaud S, Hamel S, Schweisguth F - PLoS Biol. (2005)

Expression of Neur in Dorsal Cells Is Sufficient to Rescue the D-mib Mutant PhenotypeD-mib2/D-mib3 mutant discs expressing GFP (A) (GFP staining not shown), Ser (B), Ncdc10 (C), or Neur (D) under the control of Ser-GAL4 were stained for Cut (red). Expression of Ser in dorsal cells did not rescue the D-mib2/D-mib3 wing pouch mutant phenotype (compare [B] with [A]), consistent with D-mib being required for Ser signaling. By contrast, expression of Ncdc10, an activated version of N, led to the deregulated growth of the dorsal compartment and the expression of Cut in most dorsal cells (C), indicating that activated N acts downstream of D-mib. Expression of Neur in dorsal cells was sufficient to compensate for the loss of D-mib activity (D).Bar is 40 μm for all panels.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1064853&req=5

pbio-0030096-g008: Expression of Neur in Dorsal Cells Is Sufficient to Rescue the D-mib Mutant PhenotypeD-mib2/D-mib3 mutant discs expressing GFP (A) (GFP staining not shown), Ser (B), Ncdc10 (C), or Neur (D) under the control of Ser-GAL4 were stained for Cut (red). Expression of Ser in dorsal cells did not rescue the D-mib2/D-mib3 wing pouch mutant phenotype (compare [B] with [A]), consistent with D-mib being required for Ser signaling. By contrast, expression of Ncdc10, an activated version of N, led to the deregulated growth of the dorsal compartment and the expression of Cut in most dorsal cells (C), indicating that activated N acts downstream of D-mib. Expression of Neur in dorsal cells was sufficient to compensate for the loss of D-mib activity (D).Bar is 40 μm for all panels.
Mentions: The functional assay was then used to genetically position the requirement for the D-mib gene activity relative to Ser and N (Figure 8). Expression of an activated version of N, Ncdc10 [51], led to the activation of Cut and promoted growth in dorsal cells of D-mib2/D-mib3 mutant discs (Figure 8C). This indicates that D-mib acts at a step upstream of N activation. By contrast, elevated levels of Ser expression failed to restore Cut expression and growth of the wing pouch in D-mib2/D-mib3 mutant larvae (Figure 8B). This confirms that Ser signaling requires the activity of the D-mib gene, i.e., that D-mib acts downstream of Ser.

Bottom Line: During wing development, expression of D-mib 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 D-mib gene is required for the endocytosis of Ser in wing imaginal disc cells.We conclude that D-mib and Neur are two structurally distinct proteins that have similar molecular activities but distinct developmental functions in Drosophila.

View Article: PubMed Central - PubMed

Affiliation: Ecole Normale Supérieure, CNRS UMR 8542, Paris, France.

ABSTRACT
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 Drosophila melanogaster and Danio rerio, respectively. While the neur and mib genes are evolutionarily conserved, their respective roles in the context of a single organism have not yet been examined. We show here that the Drosophila mind bomb (D-mib) gene regulates a subset of Notch signaling events, including wing margin specification, leg segmentation, and vein determination, that are distinct from those events requiring neur activity. D-mib also modulates lateral inhibition, a neur- and Dl-dependent signaling event, suggesting that D-mib regulates Dl signaling. During wing development, expression of D-mib 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 D-mib gene is required for the endocytosis of Ser in wing imaginal disc cells. Finally, ectopic expression of neur in D-mib mutant larvae rescues the wing D-mib phenotype, indicating that Neur can compensate for the lack of D-mib activity. We conclude that D-mib and Neur are two structurally distinct proteins that have similar molecular activities but distinct developmental functions in Drosophila.

Show MeSH
Related in: MedlinePlus