Limits...
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.

Show MeSH

Related in: MedlinePlus

The D-mib and neur Genes Have Distinct Functions during Wing Development(A–E) Wing imaginal discs (B–E) from wild-type (B and D), D-mib1 (C), and D-mib1/D-mib2 (E) third instar larvae stained for Cut (B and C) and wg-lacZ (D and E). D-mib mutant discs showed a dramatically reduced size of the wing pouch (see diagram in [A] showing the different regions of the wing imaginal disc; V, ventral; D, dorsal), as well as a complete loss of Cut and wg-lacZ (red arrows in [B–E]) expression at the wing margin. Expression of wg-lacZ in the hinge region (arrowheads in [D] and [E]) and the accumulation of Cut in sensory cells (small arrows in [B] and [C]) and muscle precursor cells (large arrowheads in [B] and [C]) appeared to be largely unaffected).(F and F′) Expression of Cut (red) at the wing margin was not affected by the complete loss of neur activity in neur1F65 mutant clones (indicated by the loss of the nuclear green fluorescent protein [GFP] marker, in green).Bar is 50 μm in (B–E) and 20 μm in (F and F′).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC1064853&req=5

pbio-0030096-g002: The D-mib and neur Genes Have Distinct Functions during Wing Development(A–E) Wing imaginal discs (B–E) from wild-type (B and D), D-mib1 (C), and D-mib1/D-mib2 (E) third instar larvae stained for Cut (B and C) and wg-lacZ (D and E). D-mib mutant discs showed a dramatically reduced size of the wing pouch (see diagram in [A] showing the different regions of the wing imaginal disc; V, ventral; D, dorsal), as well as a complete loss of Cut and wg-lacZ (red arrows in [B–E]) expression at the wing margin. Expression of wg-lacZ in the hinge region (arrowheads in [D] and [E]) and the accumulation of Cut in sensory cells (small arrows in [B] and [C]) and muscle precursor cells (large arrowheads in [B] and [C]) appeared to be largely unaffected).(F and F′) Expression of Cut (red) at the wing margin was not affected by the complete loss of neur activity in neur1F65 mutant clones (indicated by the loss of the nuclear green fluorescent protein [GFP] marker, in green).Bar is 50 μm in (B–E) and 20 μm in (F and F′).

Mentions: Complete loss of zygotic D-mib activity in homozygous D-mib1 and trans-heterozygous D-mib2/D-mib3, D-mib1/D-mib3 and D-mib1/D-mib2 individuals led to late pupal lethality. Mutant pupae died as pharate adults showing ectopic macrochaetes, increased microchaete density on the dorsal thorax (Figure 1I and 1J), short legs lacking tarsal segmentation (Figure 1L and 1M), and nearly complete loss of eye and wing tissues (Figure 1D and 1E). Tissue losses were associated with a dramatic reduction in size of the eye field and of the wing pouch in mutant discs of third instar larvae (Figure 2A–2E). Hypomorphic D-mib2/D-mib4 mutant flies only showed ectopic sensory organs, rough eyes, small wings, and thickened veins (Figure 1D, 1D′, 1G, and 1G′; data not shown).


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)

The D-mib and neur Genes Have Distinct Functions during Wing Development(A–E) Wing imaginal discs (B–E) from wild-type (B and D), D-mib1 (C), and D-mib1/D-mib2 (E) third instar larvae stained for Cut (B and C) and wg-lacZ (D and E). D-mib mutant discs showed a dramatically reduced size of the wing pouch (see diagram in [A] showing the different regions of the wing imaginal disc; V, ventral; D, dorsal), as well as a complete loss of Cut and wg-lacZ (red arrows in [B–E]) expression at the wing margin. Expression of wg-lacZ in the hinge region (arrowheads in [D] and [E]) and the accumulation of Cut in sensory cells (small arrows in [B] and [C]) and muscle precursor cells (large arrowheads in [B] and [C]) appeared to be largely unaffected).(F and F′) Expression of Cut (red) at the wing margin was not affected by the complete loss of neur activity in neur1F65 mutant clones (indicated by the loss of the nuclear green fluorescent protein [GFP] marker, in green).Bar is 50 μm in (B–E) and 20 μm in (F and F′).
© Copyright Policy
Related In: Results  -  Collection

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

pbio-0030096-g002: The D-mib and neur Genes Have Distinct Functions during Wing Development(A–E) Wing imaginal discs (B–E) from wild-type (B and D), D-mib1 (C), and D-mib1/D-mib2 (E) third instar larvae stained for Cut (B and C) and wg-lacZ (D and E). D-mib mutant discs showed a dramatically reduced size of the wing pouch (see diagram in [A] showing the different regions of the wing imaginal disc; V, ventral; D, dorsal), as well as a complete loss of Cut and wg-lacZ (red arrows in [B–E]) expression at the wing margin. Expression of wg-lacZ in the hinge region (arrowheads in [D] and [E]) and the accumulation of Cut in sensory cells (small arrows in [B] and [C]) and muscle precursor cells (large arrowheads in [B] and [C]) appeared to be largely unaffected).(F and F′) Expression of Cut (red) at the wing margin was not affected by the complete loss of neur activity in neur1F65 mutant clones (indicated by the loss of the nuclear green fluorescent protein [GFP] marker, in green).Bar is 50 μm in (B–E) and 20 μm in (F and F′).
Mentions: Complete loss of zygotic D-mib activity in homozygous D-mib1 and trans-heterozygous D-mib2/D-mib3, D-mib1/D-mib3 and D-mib1/D-mib2 individuals led to late pupal lethality. Mutant pupae died as pharate adults showing ectopic macrochaetes, increased microchaete density on the dorsal thorax (Figure 1I and 1J), short legs lacking tarsal segmentation (Figure 1L and 1M), and nearly complete loss of eye and wing tissues (Figure 1D and 1E). Tissue losses were associated with a dramatic reduction in size of the eye field and of the wing pouch in mutant discs of third instar larvae (Figure 2A–2E). Hypomorphic D-mib2/D-mib4 mutant flies only showed ectopic sensory organs, rough eyes, small wings, and thickened veins (Figure 1D, 1D′, 1G, and 1G′; data not shown).

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