JAK/STAT signalling in<i>Drosophila</i>: insights into conserved regulatory and cellular functions

Arbouzova, Natalia I.; Zeidler, Martin P.

doi:10.1242/dev.02411

Cited by 361 publications

(350 citation statements)

References 115 publications

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“…Signaling can be attenuated by a variety of negative regulators, including the suppressor of cytokine signaling (SOCS) proteins encoded by Socs36E and Socs44A (Rawlings et al 2004a,b;Arbouzova and Zeidler 2006). Jak/Stat signaling directs a diverse spectrum of developmental events including cell migration, proliferation, patterning, and morphogenesis (reviewed in Arbouzova andZeidler 2006 andLi 2008).…”

Section: Resultsmentioning

confidence: 99%

Retinal Axon Guidance Requires Integration of Eya and the Jak/Stat Pathway into Phosphotyrosine-Based Signaling Circuitries in Drosophila

2016

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The transcriptional coactivator and phosphatase eyes absent (Eya) is dynamically compartmentalized between the nucleus and cytoplasm. Although the nuclear transcriptional circuits within which Eya operates have been extensively characterized, understanding of its cytoplasmic functions and interactions remains limited. Our previous work showed that phosphorylation of Drosophila Eya by the Abelson tyrosine kinase can recruit Eya to the cytoplasm and that eya-abelson interactions are required for photoreceptor axons to project to correct layers in the brain. Based on these observations, we postulated that photoreceptor axon targeting might provide a suitable context for identifying the cytoplasmic signaling cascades with which Eya interacts. Using a dosesensitive eya misexpression background, we performed an RNA interference-based genetic screen to identify suppressors. Included among the top 10 hits were nonreceptor tyrosine kinases and multiple members of the Jak/Stat signaling network (hop, Stat92E, Socs36E, and Socs44A), a pathway not previously implicated in axon targeting. Individual loss-of-function phenotypes combined with analysis of axonal projections in Stat92E null clones confirmed the importance of photoreceptor autonomous Jak/Stat signaling. Experiments in cultured cells detected cytoplasmic complexes between Eya and Hop, Socs36E and Socs44A; the latter interaction required both the Src homology 2 motif in Socs44A and tyrosine phosphorylated Eya, suggesting direct binding and validating the premise of the screen. Taken together, our data provide new insight into the cytoplasmic phosphotyrosine signaling networks that operate during photoreceptor axon guidance and suggest specific points of interaction with Eya.KEYWORDS SH2; genetic screen; retinal determination network; eye development; Socs44A A remarkable feature of multicellular animal development is that the complexity and diversity in tissue type and patterning is achieved using fewer than a dozen signaling pathways, including Notch, receptor tyrosine kinase, Wnt, Hedgehog, TGFb, Jak/Stat, and Hippo. These cascades are repeatedly deployed in different contexts to regulate the majority of the critical proliferation, survival, specification, and differentiation decisions (reviewed in Voas and Rebay 2004;Housden and Perrimon 2014). One strategy to achieve context-specific developmental regulation is for proteins and pathways to function together in interconnected networks. Further, individual proteins within these networks may encode multiple independent functions that can be executed in distinct parts of the cell, cell types, or stages of development. In this way, even a modest number of individual proteins and core pathways can create vast combinatorial possibilities.Eyes absent (Eya), a protein conserved from plants to humans, presents an ideal model to study integration because its multifunctionality and dynamic subcellular localization provide opportunities for interaction with many signaling pathways (reviewed in Jemc andRebay 2007 an...

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Section: Resultsmentioning

confidence: 99%

Retinal Axon Guidance Requires Integration of Eya and the Jak/Stat Pathway into Phosphotyrosine-Based Signaling Circuitries in Drosophila

2016

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“…1E, F) (Bucher et al, 2005), as well as transcripts of genes encoding components of the JAK/STAT signalling pathway ( Fig. 1G-N) (Arbouzova and Zeidler, 2006). We did not observe an equivalent staining in pre-blastoderm embryos following in situ hybridization experiments using sense strand control probes (shown for T.c.caudal in Fig.…”

Section: In Situ Hybridization Reveals the Existence Of Polar Body-asmentioning

confidence: 96%

Early asymmetries in maternal transcript distribution associated with a cortical microtubule network and a polar body in the beetle Tribolium castaneum

Peel

Averof

2010

Developmental Dynamics

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The localization of maternal mRNAs during oogenesis plays a central role in axial specification in some insects. Here we describe a polar body-associated asymmetry in maternal transcript distribution in preblastoderm eggs of the beetle Tribolium castaneum. Since the position of the polar body marks the future dorsal side of the embryo, we have investigated whether this asymmetry in mRNA distribution plays a role in dorsal-ventral axis specification. Whilst our results suggest polar body-associated transcripts do not play a significant role in specifying the DV axis, at least during early embryogenesis, we do find that the polar body is closely associated with a cortical microtubule network (CMN), which may play a role in the localization of transcripts during oogenesis. Transcripts of the gene T.c.pangolin co-localize with the CMN at the time of their anterior localization during oogenesis and their anterior localization is disrupted by the microtubule-depolymerizing agent colcemid. Developmental Dynamics 239:2875-2887,

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“…Drosophila is an especially suitable model organism with which to address this question not only because its repertoire of cytokines is significantly reduced but also because the signaling pathways regulated by these cytokines are similarly simplified (4). A large number of mammalian cytokines, including interleukins and interferons, modulate transcription by recruiting the JAK/ STAT signaling pathway.…”

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confidence: 99%

Cytokine signaling through the JAK/STAT pathway is required for long-term memory in Drosophila

Copf

Goguel²,

Lampin-Saint-Amaux³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Cytokine signaling through the JAK/STAT pathway regulates multiple cellular responses, including cell survival, differentiation, and motility. Although significant attention has been focused on the role of cytokines during inflammation and immunity, it has become clear that they are also implicated in normal brain function. However, because of the large number of different genes encoding cytokines and their receptors in mammals, the precise role of cytokines in brain physiology has been difficult to decipher. Here, we took advantage of Drosophila's being a genetically simpler model system to address the function of cytokines in memory formation. Expression analysis showed that the cytokine Upd is enriched in the Drosophila memory center, the mushroom bodies. Using tissue-and adult-specific expression of RNAi and dominantnegative proteins, we show that not only is Upd specifically required in the mushroom bodies for olfactory aversive long-term memory but the Upd receptor Dome, as well as the Drosophila JAK and STAT homologs Hop and Stat92E, are also required, while being dispensable for less stable memory forms.

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JAK/STAT signalling inDrosophila: insights into conserved regulatory and cellular functions

Cited by 361 publications

References 115 publications

Retinal Axon Guidance Requires Integration of Eya and the Jak/Stat Pathway into Phosphotyrosine-Based Signaling Circuitries in Drosophila

Retinal Axon Guidance Requires Integration of Eya and the Jak/Stat Pathway into Phosphotyrosine-Based Signaling Circuitries in Drosophila

Early asymmetries in maternal transcript distribution associated with a cortical microtubule network and a polar body in the beetle Tribolium castaneum

Cytokine signaling through the JAK/STAT pathway is required for long-term memory in Drosophila

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