Enhancer ofSplit [E(spl)D] is a gro-independent, hypermorphic mutation inDrosophila

Nagel, Anja C.; Yu, Yong; Preiss, Anette

doi:10.1002/(sici)1520-6408(1999)25:2<168::aid-dvg11>3.0.co;2-0

Cited by 16 publications

(11 citation statements)

References 31 publications

(65 reference statements)

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“…3a). As expected, and previously described (Nagel et al , 1999), expression of M8* elicited a severely reduced eye in N spl /Y animals (Fig. 3g).…”

Section: Resultssupporting

confidence: 92%

“…We describe here the unexpected antimorphic activity of this variant, which we call M8SDΔGro. In N + flies, M8SDΔGro elicits supernumerary (ectopic) bristles and potently suppresses the bristle loss phenotype of ectopic M8, but does not interfere with R8 specification or eye development, effects similar to those reported for M8* (Giebel and Campos-Ortega, 1997; Nagel et al , 1999). However, M8SDΔGro and M8* behave very differently in the N spl background.…”

Section: Introductionsupporting

confidence: 52%

“…For in vivo analysis, we generated multiple independent insertions of UAS-constructs encoding all three constructs (Fig. 2a); the single insertion of UAS-m8 * has been previously used by others and us (Karandikar et al , 2004; Nagel et al , 1999). …”

Section: Resultsmentioning

confidence: 99%

“…This mutation encodes a truncated protein (M8*) and increases transcript stability in the MF of the eye disc, the site of expression of endogenous m8 (Nagel and Preiss, 1999). Despite its inability to bind Gro, M8* severely impairs eye development in the presence of N spl , leading to the proposal that E(spl)D is a gro -independent hypermorph (Nagel et al , 1999). This possibility is enigmatic since Gro is esential for repression.…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, over-expression of a UAS-m8 * construct during eye development mimics the effects of E(spl)D , indicating that the truncation in M8* underlies its enhancement of N spl . It has, therefore, been suggested that E(spl)D is a gro -independent hypermorph (Nagel et al , 1999). However, in N + flies, M8* acts as an antimorph and elicits ectopic bristles, an unexpected finding since removal of the C-terminal tetrapeptide WRPW per se from full-length M8 renders the protein non-functional (Giebel and Campos-Ortega, 1997).…”

Section: Introductionmentioning

confidence: 99%

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On the mechanism underlying the divergent retinal and bristle defects of M8* (E(spl)D) in Drosophila

Kahali

Bose

Karandikar

et al. 2009

Genesis

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Our results, using endogenous mutants and Gal4-UAS driven transgenes, implicate multisite phosphorylation in repression by E(spl)M8. We propose that these phosphorylations occur in the morphogenetic furrow (MF) to reverse an auto-inhibited state of M8, enabling repression of Atonal during R8 specification. Our studies address the paradoxical behavior of M8*, the truncated protein encoded by E(spl)D. We suggest that differences in N signaling in the bristle versus the eye underlie the antimorphic activity of M8* in N + (ectopic bristles) and hypermorphic activity in N spl (reduced eye). Ectopic M8* impairs eye development (in N spl ) only during establishment of the atonal feedback loop (anterior to the MF), but is ineffective after this time point. In contrast, a CK2 phosphomimetic M8 lacking Groucho (Gro) binding, M8SDΔGro, acts antimorphic in N + and suppresses the eye/R8 and bristle defects of N spl , as does reduced dosage of E(spl) or CK2. Multisite phosphorylation could serve as a checkpoint to enable a precise onset of repression, and this is bypassed in M8*. Additional implications are discussed.

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“…3a). As expected, and previously described (Nagel et al , 1999), expression of M8* elicited a severely reduced eye in N spl /Y animals (Fig. 3g).…”

Section: Resultssupporting

confidence: 92%

Section: Introductionsupporting

confidence: 52%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

On the mechanism underlying the divergent retinal and bristle defects of M8* (E(spl)D) in Drosophila

Kahali

Bose

Karandikar

et al. 2009

Genesis

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New tool for an old problem: can RNAi efficiently resolve the issue of genetic redundancy?

Kan

Kessler

2004

Bioessays

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RNA interference (RNAi) has become a generally accepted tool for inhibiting gene expression in many laboratory organisms. Nagel et al.,(1) in a recent paper, give an example of how this tool can also be used to address the question of genetic redundancy. Their focus was on the redundancy in Drosophila melanogaster of the Enhancer of split gene complex [E(spl)-C] which comprises seven highly related genes. Their somewhat conflicting findings are probably the typical scenario for most RNAi experiments: some expected results and some surprises.

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Evidence that the C‐terminal domain (CtD) autoinhibits neural repression by Drosophila E(spl)M8

Kahali

Kim

Karandikar

et al. 2009

Genesis

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Analysis of the retinal defects of a CK2 phosphomimetic variant of E(spl)M8 (M8S(159)D) and the truncated protein M8* encoded by the E(spl)D allele, suggest that the nonphosphorylated CtD "autoinhibits" repression. We have investigated this model by testing for inhibition (in "trans") by the CtD fragment in its nonphosphorylated (M8-CtD) and phosphomimetic (M8SD-CtD) states. In N(+) flies, ectopic M8-CtD compromises lateral inhibition, i.e., elicits supernumerary bristles as with loss of N signaling. This antimorphic activity of M8-CtD strongly rescues the reduced eye and/or bristle loss phenotypes that are elicited by ectopic M8SD or wild type M8. Additionally, the severely reduced eye of N(spl)/Y; E(spl)D/+ flies is also rescued by M8-CtD. Rescue is specific to the time and place, the morphogenetic furrow, where "founding" R8 photoreceptors are specified. In contrast, the phosphomimetic M8SD-CtD that is predicted to be deficient for autoinhibition, exhibits significantly attenuated or negligible activity. These studies provide evidence that autoinhibition by the CtD regulates M8 activity in a phosphorylation-dependent manner.

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Enhancer ofSplit [E(spl)D] is a gro-independent, hypermorphic mutation inDrosophila

Cited by 16 publications

References 31 publications

On the mechanism underlying the divergent retinal and bristle defects of M8* (E(spl)D) in Drosophila

On the mechanism underlying the divergent retinal and bristle defects of M8* (E(spl)D) in Drosophila

New tool for an old problem: can RNAi efficiently resolve the issue of genetic redundancy?

Evidence that the C‐terminal domain (CtD) autoinhibits neural repression by Drosophila E(spl)M8

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