Control of development and immunity by Rel transcription factors in Drosophila

Govind, Shubha

doi:10.1038/sj.onc.1203223

Cited by 105 publications

(74 citation statements)

References 146 publications

(154 reference statements)

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“…Many mutants show increased lamellocyte numbers and form melanotic masses, ''pseudotumors,'' in what is probably an overreaction of the cellular immune response (18,19). Notably, mutations that activate the Toll and Jak͞Stat pathways show this phenotype, suggesting an important role for these pathways in the cellular response (20)(21)(22)(23). Furthermore, Notch function is required for a normal cellular response (16).…”

mentioning

confidence: 99%

A directed screen for genes involved in Drosophila blood cell activation

Zettervall

Ines

Williams

et al. 2004

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

323

400

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An attack by a parasitic wasp activates a vigorous cellular immune response in Drosophila larvae. This response is manifested by an increased number of circulating cells, the hemocytes, and by the appearance of a specialized class of hemocyte, the lamellocytes, which participate in the encapsulation and killing of the parasite. To study the molecular mechanisms of this response, we have overexpressed different genes in the hemocytes, by using the GAL4-upstream activating sequence system and a hemocytespecific Hemese-GAL4 driver. Multiple transgenes were tested, representing several important signaling pathways. We found that the proliferation response and the activation of lamellocyte formation are independent phenomena. A drastic increase in the number of circulating hemocytes is caused by receptor tyrosine kinases, such as Egfr, Pvr, and Alk, as well as by the downstream signaling components Ras85D and pointed, supporting the notion that the Ras-mitogen-activated protein kinase pathway regulates hemocyte numbers. In the case of Pvr and Alk, this phenotype also is accompanied by lamellocyte formation. By contrast, constitutively active hopscotch and hemipterous give massive activation of lamellocyte formation with little or no increase in total hemocyte numbers. This finding indicates that both the Jak͞Stat and the Jun kinase pathways affect lamellocyte formation. Still other signals, mediated by aop ACT , Toll 10b , and Rac1 expression, cause a simultaneous increase in lamellocyte and total cell numbers, and the same effect is seen when WNT signaling is suppressed. We conclude that the activation of a cellular response is complex and affected by multiple signaling pathways.

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mentioning

confidence: 99%

A directed screen for genes involved in Drosophila blood cell activation

Zettervall

Ines

Williams

et al. 2004

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

323

400

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“…However members of the NF-jB family have also been demonstrated to act as important regulators of early Drosophila development (Govind, 1999). Such dualist roles for NF-jB in immunity and development have led to intense investigation on the signalling pathways that regulate its activation.…”

Section: Resultsmentioning

confidence: 99%

“…The proteolysis of I-jBs allows for nuclear translocation of NF-jB and its activation of transcription of a plethora of genes including ones that promote the generation of dorso-ventral polarity in early development. Given the highly conserved nature of the NF-jB/I-jB families Drosophila has served as a highly valuable model organism in defining the early developmental role of NF-jB (Govind, 1999;Minakhina and Steward, 2006). Thus dorsal, the NF-jB homologue in Drosophila, is regulated by the I-jB family member Cactus and the activation of dorsal drives dorso-ventral polarity formation in developing Drosophila.…”

Section: Resultsmentioning

confidence: 99%

Characterisation of expression patterns and functional role of Cactin in early zebrafish development

Atzei

Yang

Collery

et al. 2010

Gene Expression Patterns

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a b s t r a c tThe immune system of teleost zebrafish (Danio rerio) shows high similarity to mammalian counterparts sharing many innate immune components including Toll-Like Receptors (TLRs), cytokines, chemokines and complement molecules. As in mammals, zebrafish also contains the transcription factor NF-jB that plays dualist roles in innate immunity and early development. Indeed NF-jB members are expressed in different temporal patterns during the early stages of zebrafish embryogenesis indicating that each molecule is involved in specific developmental events. In the present study we employ zebrafish as a model to characterise the expression pattern and role of a novel NF-jB regulator, termed Cactin, in early development. Cactin was first characterised in Drosophila as a new member of the Rel pathway that could affect the generation of dorsal-ventral polarity. To explore the potential developmental role of Cactin in zebrafish, we initially investigated its expression pattern and functional role during early embryonic developmental stages. We detect Cactin expression at all stages of early development and knockdown of Cactin by specific morpholino antisense oligonucleotides causes developmental abnormalities manifested by an overall dysmorphic cellular organisation. These results indicate that Cactin has been highly conserved during evolution and plays a key role in early embryonic development.

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“…It is of interest that the Drosophila NF-B/Rel factor Dorsal has been shown to be directly involved in the specification of embryonic dorsal/ventral polarity (reviewed in Ref. 45). Although intrinsically a transcriptional activator, Dorsal can function as a repressor by recruiting transcription repressors to negative response elements.…”

Section: Transcriptional Activity Of the Promoter Regions Of The Aldhmentioning

confidence: 99%

Differential Regulation of the Aldehyde Dehydrogenase 1 Gene in Embryonic Chick Retina and Liver

Godbout

Monckton

2001

Journal of Biological Chemistry

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Aldehyde dehydrogenase (ALDH1) is highly expressed in the dorsal cells of the undifferentiated retina, where it has been proposed to play a role in the formation of a retinoic acid gradient along the ventrodorsal axis. In contrast to the retina, ALDH1 levels increase with differentiation in the liver and remain elevated in the adult tissue. To understand the molecular basis for differential expression of ALDH1 during development, we characterized the ALDH1 transcripts expressed in chick retina and liver. By sequencing, primer extension, and S1 nuclease analysis, we show that retina ALDH1 mRNA has an additional 300 nucleotides of 5-untranslated sequence resulting from the transcription of two 5 noncoding exons. There is a 24 -29-kilobase pair (kb) gap between exons 1 and 2 and a 290-base pair gap between exons 2 and 3. Exon 3, which contains the ALDH1 start codon, represents the first exon of the liver transcript. Using a reporter gene assay, we have identified tissuespecific regulatory elements that govern ALDH1 expression in primary retina and liver cultures. Constructs with >1.6 kb of DNA flanking the 5-end of exon 1 showed elevated activity in retinal cultures but only basal activity in liver cultures. In contrast, constructs with <1 kb of 5-flanking DNA were active in both retina and liver cultures. Our results suggest that an important mechanism for the control of ALDH1 transcriptional activity is through the presence of inhibitory elements located 0.7-1.6 kb upstream of the ALDH1 gene. DNase I footprint analysis reveal four sites of protein-DNA interaction within this region, one of which is specific to the liver and corresponds to a NF-B/Rel binding site.

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Control of development and immunity by Rel transcription factors in Drosophila

Cited by 105 publications

References 146 publications

A directed screen for genes involved in Drosophila blood cell activation

A directed screen for genes involved in Drosophila blood cell activation

Characterisation of expression patterns and functional role of Cactin in early zebrafish development

Differential Regulation of the Aldehyde Dehydrogenase 1 Gene in Embryonic Chick Retina and Liver

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