A Novel Interaction Between <i>hedgehog</i> and <i>Notch</i> Promotes Proliferation at the Anterior–Posterior Organizer of the Drosophila Wing

Casso, David J.; Biehs, Brian; Kornberg, Thomas B.

doi:10.1534/genetics.110.125138

Cited by 18 publications

(12 citation statements)

References 75 publications

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“…Using a ubiquitous driver, we first confirmed that our Psn shRNA lines result in 80-90% reduction of mRNA levels (Figure 1) and recapitulate developmental phenotypes of Psn germ-line mutant flies (Struhl and Greenwald 1999;Chung and Struhl 2001;Mahoney et al 2006). Consistent with notching wings in Notch heterozygous mutant flies, and in wing-specific Notch or Psn KD flies (Boyles et al 2010;Casso et al 2011), wing disc-specific expression of Psn shRNA leads to similar wing phenotypes at varying severity, allowing selection of the most effective Psn shRNA line (Figure 2). Selective neuronal expression of two independent Psn shRNA lines beginning at embryonic stages caused earlier lethality, rough eye phenotypes, and severe climbing defects (Figure 3 and Figure 4), and these phenotypes were partially rescued by expressing a Drosophila Psn transgene ( Figure 5).…”

Section: Discussionsupporting

confidence: 64%

An Evolutionarily Conserved Role of Presenilin in Neuronal Protection in the Aging Drosophila Brain

et al. 2017

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Mutations in the genes are the major genetic cause of Alzheimer's disease. Presenilin and Nicastrin are essential components of γ-secretase, a multi-subunit protease that cleaves Type I transmembrane proteins. Genetic studies in mice previously demonstrated that conditional inactivation of Presenilin or Nicastrin in excitatory neurons of the postnatal forebrain results in memory deficits, synaptic impairment, and age-dependent neurodegeneration. The roles of () and () in the adult fly brain, however, are unknown. To knockdown (KD) or selectively in neurons of the adult brain, we generated multiple shRNA lines. Using a ubiquitous driver, these shRNA lines resulted in 80-90% reduction of mRNA and pupal lethality-a phenotype that is shared with and mutants carrying nonsense mutations. Furthermore, expression of these shRNAs in the wing disc caused notching wing phenotypes, which are also shared with and mutants. Similar to , neuron-specific KD using two independent shRNA lines led to early mortality and rough eye phenotypes, which were rescued by a fly transgene. Interestingly, conditional KD (cKD) of or in adult neurons using the and system caused shortened lifespan, climbing defects, increases in apoptosis, and age-dependent neurodegeneration. Together, these findings demonstrate that, similar to their mammalian counterparts, Psn and Nct are required for neuronal survival during aging and normal lifespan, highlighting an evolutionarily conserved role of Presenilin in neuronal protection in the aging brain.

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Section: Discussionsupporting

confidence: 64%

An Evolutionarily Conserved Role of Presenilin in Neuronal Protection in the Aging Drosophila Brain

et al. 2017

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“…Notch was first identified in Drosophila as an important gene for wing development (de Celis and GarciaBellido, 1994). It is required for the establishment of the dorsal-ventral compartment border, and the proper development of wing margin, veins, and sensory organs (Casso et al, 2011). The Notch receptor is activated by the Delta and Jagged/Serrate families of membrane-bound ligands (Weinmaster, 1997).…”

Section: Introductionmentioning

confidence: 99%

A broad expression profile of the GMR-GAL4 driver in Drosophila melanogaster

Li¹,

Sl²,

Hy³

et al. 2012

Genet. Mol. Res.

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ABSTRACT. The GAL4/UAS binary system has been widely used in Drosophila melanogaster for ectopic expression of transgenes in a tissue-specific manner. The GMR-GAL4 driver, which expresses the yeast transcription factor GAL4 under the control of glass multiple reporter (GMR) promoter elements, has been commonly utilized to express target transgenes, specifically in the developing eye. However, we have observed abnormal wing phenotypes; this is a result of the activity of critical wing developing genes, e.g., components of the Notch or Wg pathway, that are up-or down-regulated under the control of the GMR-GAL4 driver. X-gal staining confirmed that UAS-LacZ is expressed in third-instar larva wing imaginal discs, as well as in eye discs, when driven by the GMR-GAL4 driver. Furthermore, we found that GMR-GAL4 also drives UAS-LacZ expression in other tissues, such as brain, trachea, and leg discs. These results indicate that GMR-GAL4 has a broad expression profile, rather than the eye-specific pattern described previously, and that one should be careful when using it as a tool for targeted gene expression.

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“…Both the notum and anterior wing margin primordia are predominantly in the A compartment, and genes that are known to function in neuronal development (such as acheate and scute ) are therefore expected to be expressed at high levels in A cells. Furthermore, because A cells at the A/P compartment border depend upon activation of the Notch pathway (Casso et al 2011), Notch pathway components might also be expressed in greater levels in A cells. The A subcluster from the array analysis did include achaete and scute as well as the Notch pathway components Enhancer of spilt complex transcripts m7 , m4 , and γ.…”

Section: Resultsmentioning

confidence: 99%

Microarray Comparison of Anterior and PosteriorDrosophilaWing Imaginal Disc Cells Identifies Novel Wing Genes

Ibrahim

Biehs

Kornberg

et al. 2013

G3 Genes|Genomes|Genetics

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Signaling between cells in the anterior (A) and posterior (P) compartments directs Drosophila wing disc development and is dependent on expression of the homeodomain transcription factor Engrailed (En) in P cells. Downstream of en, posteriorly expressed Hedgehog (Hh) protein signals across the A/P border to establish a developmental organizer that directs pattern formation and growth throughout the wing primordium. Here we extend investigations of the processes downstream of en by using expression array analysis to compare A and P cells. A total of 102 candidate genes were identified that express differentially in the A and P compartments; four were characterized: Stubble (Sb) expression is restricted to A cells due to repression by en. CG15905, CG16884; CG10200/hase und igel (hui) are expressed in A cells downstream of Hh signaling; and RNA interference for hui, Stubble, and CG16884 revealed that each is essential to wing development.

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A Novel Interaction Between hedgehog and Notch Promotes Proliferation at the Anterior–Posterior Organizer of the Drosophila Wing

Cited by 18 publications

References 75 publications

An Evolutionarily Conserved Role of Presenilin in Neuronal Protection in the Aging Drosophila Brain

An Evolutionarily Conserved Role of Presenilin in Neuronal Protection in the Aging Drosophila Brain

A broad expression profile of the GMR-GAL4 driver in Drosophila melanogaster

Microarray Comparison of Anterior and PosteriorDrosophilaWing Imaginal Disc Cells Identifies Novel Wing Genes

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