Searching for the prototypic eye genetic network:
            <i>Sine oculis</i>
            is essential for eye regeneration in planarians

Pineda, David; González, Javier; Callaerts, Patrick; Ikeo, Kazuho; Gehring, W.J.; Saló, Emili

doi:10.1073/pnas.97.9.4525

Cited by 144 publications

(85 citation statements)

References 29 publications

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“…Although most cells possess the basic RNAi core machinery, some cell types have the intriguing ability to naturally take up exogenous dsRNA and use it to initiate RNAi silencing 2,3,[5][6][7] . Furthermore, some organisms, such as plants, C. elegans and planaria (Girardia tigrina) can transmit the RNA silencing signal from cell to cell, resulting in the systemic spread of the RNAi response 8,26,29,30 . It is currently believed that insects lack a pathway for the systemic spreading of RNAi.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the basic machinery that mediates dsRNA upake in Drosophila is also required for systemic spread of the RNAi signal in C. elegans, suggesting that the dsRNA entry pathway is evolutionarily conserved and functionally relevant in intact organisms. 8,26,29,30 . It is currently believed that insects lack a pathway for the systemic spreading of RNAi.…”

Section: Conservation Of Entry Pathways Between Drosophila and C Elementioning

confidence: 99%

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The endocytic pathway mediates cell entry of dsRNA to induce RNAi silencing

et al. 2006

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Many metazoan cells can take up exogenous double-stranded (ds) RNA and use it to initiate an RNA silencing response, however, the mechanism for this uptake is ill-defined. Here, we identify the pathway for dsRNA uptake in Drosophila melanogaster S2 cells. Biochemical and cell biological analyses, and a genome-wide screen for components of the dsRNA-uptake machinery, indicated that dsRNA is taken up by an active process involving receptor-mediated endocytosis. Pharmacological inhibition of endocytic pathways disrupted exogenous dsRNA entry and the induction of gene silencing. This dsRNA uptake mechanism seems to be evolutionarily conserved, as knockdown of orthologues in Caenorhabditis elegans inactivated the RNA interference response in worms. Thus, this entry pathway is required for systemic RNA silencing in whole organisms. In Drosophila cells, pharmacological evidence suggests that dsRNA entry is mediated by pattern-recognition receptors. The possible role of these receptors in dsRNA entry may link RNA interference (RNAi) silencing to other innate immune responses.RNAi is a highly conserved dsRNA-guided mechanism that mediates sequence-specific gene silencing 1 . A number of animal cells can naturally take up exogenous dsRNA and use it to initiate RNAi silencing 2,3 . In some organisms, such as Drosophila, certain cells can efficiently take up dsRNA but seem to be unable to transmit this dsRNA to other cells in the body 4 . dsRNA uptake without further transmission to other cells has also been reported for some mammalian cell types [5][6][7] . Other organisms (such as C. elegans or juvenile grasshoppers) can both take up dsRNA and spread it systemically to elicit an RNAi response throughout the entire animal 8,9 . The mechanisms of uptake and spread of dsRNA are poorly understood. It is unclear whether dsRNA enters cells through passive, non-specific mechanisms, or whether there is an active mechanism that controls entry. Genetic analysis to identify genes involved in systemic spread of dsRNA in C. elegans isolated several mutants unable to distribute an ingested dsRNA signal from the gut throughout the body 8,10,11 . One of these, SID-1 (also known as RSD-8) is a putative transmembrane protein required for systemic spread 8 . When expressed ectopically in Drosophila cells, SID-1 enhanced the RNAi response observed at low dsRNA 5Correspondence should be addressed to R.A. (e-mail: Raul.Andino@UCSF.edu). 3 Current address: Canada Research Chair in Innate Immunity, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada 4 These authors contributed equally to this work.Note: Supplementary Information is available on the Nature Cell Biology website. COMPETING FINANCIAL INTERESTSThe authors declare that they have no competing financial interests. concentrations 12 , raising the possibility that SID-1 may function as a channel on the cell surface for uptake of dsRNA. However, endogenous sid-1 homologues have not been found in the Drosophila genome, yet Drosophila S2 cells...

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Section: Discussionmentioning

confidence: 99%

Section: Conservation Of Entry Pathways Between Drosophila and C Elementioning

confidence: 99%

The endocytic pathway mediates cell entry of dsRNA to induce RNAi silencing

et al. 2006

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“…Goto et al [15] reported that knockdown in fruitflies following direct injection of dsRNA lasted for at least 1 week [15]. In the planarian Girardia tigrina the RNAi effect on targeted transcript was apparent up to 3 weeks post-injection as determined by in situ hybridization [43]. In general, the mechanisms explaining longevity of the RNAi effect remain unknown.…”

Section: Discussionmentioning

confidence: 99%

In vivo and in vitro knockdown of FREP2 gene expression in the snail Biomphalaria glabrata using RNA interference

Jiang

Loker

Zhang

2006

Developmental & Comparative Immunology

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RNA interference (RNAi) is reported here for the first time for Biomphalaria glabrata, the snail intermediate host for the human parasite Schistosoma mansoni. The fibrinogen-related protein 2 (FREP2) gene, normally expressed at increased levels following exposure to digenetic trematode parasites, such as S. mansoni or Echinostoma paraensei, was targeted for knockdown. Doublestranded RNA (dsRNA) corresponding to specific regions of the FREP2 gene was introduced into snails by direct injection into the hemolymph, 2 days prior to exposure to trematodes, or added to co-cultures of B. glabrata embryonic (Bge) cells and E. paraensei sporocysts. After introduction of FREP2 dsRNA, expression levels of FREP2 were significantly reduced, to 20-30% of control values. In addition, we were able to disrupt expression of the house-keeping myoglobin gene, further confirming the feasibility of RNAi for B. glabrata. Cross-reactivity in RNAi has not been observed either among four FREP gene subfamilies or between FREP2 and myoglobin. Establishment of RNAi techniques in B. glabrata provides an important tool for clarifying the function of genes believed to play a role in host-parasite interactions, specifically between B. glabrata and its trematode parasites, including S. mansoni.

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“…However, the Drosophila gene optix, which is more closely related to so than Six 3, is capable of inducing ectopic eyes by an eyeless-independent mechanism (25). In planarians, Pax 6 participates in eye development (26), and the sine oculis homolog is essential for eye regeneration (27), suggesting that the basic elements of the genetic pathway are conserved in these prototypic eyes. These observations have suggested that the regulatory network has been adapted to the control of development of different eye types during evolution (28).…”

mentioning

confidence: 99%

Conservation of Pax 6 function and upstream activation by Notch signaling in eye development of frogs and flies

Onuma

Takahashi

Asashima

et al. 2002

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

119

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Loss of Pax 6 function leads to an eyeless phenotype in both mammals and insects, and ectopic expression of both the Drosophila and the mouse gene leads to the induction of ectopic eyes in Drosophila, which suggested to us that Pax 6 might be a universal master control gene for eye morphogenesis. Here, we report the reciprocal experiment in which the RNAs of the Drosophila Pax 6 homologs, eyeless and twin of eyeless, are transferred into a vertebrate embryo; i.e., early Xenopus embryos at the 2-and 16-cell stages. In both cases, ectopic eye structures are formed. To understand the genetic program specifying eye morphogenesis, we have analyzed the regulatory mechanisms of Pax 6 expression that initiates eye development. Previously, we have demonstrated that Notch signaling regulates the expression of eyeless and twin of eyeless in Drosophila. Here, we show that in Xenopus, activation of Notch signaling also induces eye-related gene expression, including Pax 6, in isolated animal caps. In Xenopus embryos, the activation of Notch signaling causes eye duplications and proximal eye defects, which are also induced by overexpression of eyeless and twin of eyeless. These findings indicate that the gene regulatory cascade is similar in vertebrates and invertebrates.

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Searching for the prototypic eye genetic network: Sine oculis is essential for eye regeneration in planarians

Cited by 144 publications

References 29 publications

The endocytic pathway mediates cell entry of dsRNA to induce RNAi silencing

The endocytic pathway mediates cell entry of dsRNA to induce RNAi silencing

In vivo and in vitro knockdown of FREP2 gene expression in the snail Biomphalaria glabrata using RNA interference

Conservation of Pax 6 function and upstream activation by Notch signaling in eye development of frogs and flies

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