A Screen for Genes That Influence Fibroblast Growth Factor Signal Transduction in Drosophila

Zhu, Min; Wilson, Robert; Leptin, Maria

doi:10.1534/genetics.104.039750

Cited by 32 publications

(28 citation statements)

References 35 publications

(4 reference statements)

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“…Several studies have shown that misexpression of MESR4 can modify the signaling pathway activated by fibroblast growth factor, PDGF/VEGF-like growth factor, Rac, or Cdc42 (Raymond et al, 2004;Zhu et al, 2005). Overexpression of MESR4 alone causes various defects in the adult fly morphology, such as loss of macrocheatae and dorsal thorax cleft (Abdelilah-Seyfried et al, 2000;Pena-Rangel et al, 2002).…”

Section: Resultsmentioning

confidence: 99%

The plant homeodomain finger protein MESR4 is essential for embryonic development in Drosophila

Seong

Tsuda

Tsuda‐Sakurai

et al. 2015

Genesis

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Misexpression Suppressor of Ras 4 (MESR4), a plant homeodomain (PHD) finger protein with nine zinc-finger motifs has been implicated in various biological processes including the regulation of fat storage and innate immunity in Drosophila. However, the role of MESR4 in the context of development remains unclear. Here it is shown that MESR4 is a nuclear protein essential for embryonic development. Immunostaining of polytene chromosomes using anti-MESR4 antibody revealed that MESR4 binds to numerous bands along the chromosome arms. The most intense signal was detected at the 39E-F region, which is known to contain the histone gene cluster. P-element insertions in the MESR4 locus, which were homozygous lethal during embryogenesis with defects in ventral ectoderm formation and head encapsulation was identified. In the mutant embryos, expression of Fasciclin 3 (Fas3), an EGFR signal target gene was greatly reduced, and the level of EGFR signal-dependent double phosphorylated ERK (dp-ERK) remained low. However, in the context of wing vein formation, genetic interaction experiments suggested that MESR4 is involved in the EGFR signaling as a negative regulator. These results suggested that MESR4 is a novel chromatin-binding protein required for proper expression of genes including those regulated by the EGFR signaling pathway during development. genesis 53:701-708, 2015. © 2015 Wiley Periodicals, Inc.

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Section: Resultsmentioning

confidence: 99%

The plant homeodomain finger protein MESR4 is essential for embryonic development in Drosophila

Seong

Tsuda

Tsuda‐Sakurai

et al. 2015

Genesis

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“…For example, a genetic screen for modifiers of RTK signaling in the Drosophila eye uncovered a number of genes specific to FGF receptor signaling, or common to both FGF receptor and PVR signaling but not to EGF receptor activation (Zhu et al 2005). During Drosophila oogenesis, EGFR and PVR appear to have overlapping but not identical functions in follicle cell migration (Duchek et al 2001), while cell proliferation and survival in the developing Drosophila larval dorsal thoracic air sac requires the EGF receptor but not FGF receptor signaling (Cabernard and Affolter 2005).…”

Section: Resultsmentioning

confidence: 99%

Identification of Receptor-Tyrosine-Kinase-Signaling Target Genes Reveals Receptor-Specific Activities and Pathway Branchpoints During Drosophila Development

Leatherbarrow

Halfon²

2009

Genetics

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Receptor tyrosine kinases (RTKs) are an important family of signaling molecules with the unusual property that they are able to transduce their signals using the same downstream pathways. This has led to an unresolved debate as to whether individual receptors are interchangeable, or if each receptor can mediate specific downstream responses. To address this question, we have conducted a screen to identify target genes whose expression is differentially modulated by RTKs and their downstream pathway components. Using whole-mount in situ hybridization in Drosophila embryos exposed to constitutively active RTK pathway signaling, along with quantitative RT-PCR, we found that a significant fraction of target genes respond differentially in a spatial and/or quantitative manner. This includes differential responses to EGF receptor vs. fibroblast growth factor receptor signaling as well as to more downstream components such as Ras1 and pointed. We show that not only genes but also individual alternative transcripts can respond differently to signaling, and we present evidence that the differential responses can be mediated at the transcriptional level. Our results demonstrate that different RTKs can elicit distinct transcriptional responses, and the target genes obtained from our screen provide a valuable resource for further exploration of the mechanisms underlying this signaling specificity.

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“…S3 in the supplementary material). By contrast, halving the dose of fas2 suppressed the phenotype caused by misexpression in the eye of an activated form of the FGF receptor Breathless in conjunction with Downstream-of-FGF-receptor (Dof) (Zhu et al, 2005) (see Fig. S3 in the supplementary material).…”

Section: Specificity Of Interaction Between Egfr and Fas2mentioning

confidence: 99%

Fasciclin 2, theDrosophilaorthologue of neural cell-adhesion molecule, inhibits EGF receptor signalling

Mao

Freeman

2009

Development

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Adhesion proteins not only control the degree to which cells adhere to each other but are increasingly recognised as regulators of intercellular signalling. Using genetic screening in Drosophila, we have identified Fasciclin 2 (Fas2), the Drosophila orthologue of neural cell adhesion molecule (NCAM), as a physiologically significant and specific inhibitor of epidermal growth factor receptor (EGFR) signalling in development. We find that loss of fas2 genetically interacts with multiple genetic conditions that perturb EGFR signalling. Fas2 is expressed in dynamic patterns during imaginal disc development, and in the eye we have shown that this depends on EGFR activity, implying participation in a negative-feedback loop. Loss of fas2 causes characteristic EGFR hyperactivity phenotypes in the eye, notum and wing, and also leads to downregulation of Yan, a transcriptional repressor targeted for degradation by EGFR activity. No significant genetic interactions were detected with the Notch, Wingless, Hedgehog or Dpp pathways, nor did Fas2 inhibit the FGF receptor or Torso, indicating specificity in the inhibitory role of Fas2 in EGFR signalling. Our results introduce a new regulatory interaction between an adhesion protein and a Drosophila signalling pathway and highlight the extent to which the EGFR pathway must be regulated at multiple levels.

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A Screen for Genes That Influence Fibroblast Growth Factor Signal Transduction in Drosophila

Cited by 32 publications

References 35 publications

The plant homeodomain finger protein MESR4 is essential for embryonic development in Drosophila

The plant homeodomain finger protein MESR4 is essential for embryonic development in Drosophila

Identification of Receptor-Tyrosine-Kinase-Signaling Target Genes Reveals Receptor-Specific Activities and Pathway Branchpoints During Drosophila Development

Fasciclin 2, theDrosophilaorthologue of neural cell-adhesion molecule, inhibits EGF receptor signalling

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