Conserved Expression Signatures between Medaka and Human Pigment Cell Tumors

Schartl, Manfred; Kneitz, Susanne; Wilde, Brigitta; Wagner, Toni U.; Henkel, Christiaan V.; Spaink, Herman P.; Meierjohann, Svenja

doi:10.1371/journal.pone.0037880

Cited by 35 publications

(38 citation statements)

References 46 publications

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“…Log 2 FC and P values were computed for each gene. If log 2 FC more than 1 and P value less than 0.05, genes were considered to be differentially expressed (Schartl et al 2012). …”

Section: Methodsmentioning

confidence: 99%

Evolution of the Eye Transcriptome under Constant Darkness in Sinocyclocheilus Cavefish

Meng¹,

Braasch²,

Phillips³

et al. 2013

Molecular Biology and Evolution

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In adaptating to perpetual darkness, cave species gradually lose eyes and body pigmentation and evolve alternatives for exploring their environments. Although troglodyte features evolved independently many times in cavefish, we do not yet know whether independent evolution of these characters involves common genetic mechanisms. Surface-dwelling and many cave-dwelling species make the freshwater teleost genus Sinocyclocheilus an excellent model for studying the evolution of adaptations to life in constant darkness. We compared the mature retinal histology of surface and cave species in Sinocyclocheilus and found that adult cavefish showed a reduction in the number and length of photoreceptor cells. To identify genes and genetic pathways that evolved in constant darkness, we used RNA-seq to compare eyes of surface and cave species. De novo transcriptome assemblies were developed for both species, and contigs were annotated with gene ontology. Results from cave-dwelling Sinocyclocheilus revealed reduced transcription of phototransduction and other genes important for retinal function. In contrast to the blind Mexican tetra cavefish Astyanax mexicanus, our results on morphologies and gene expression suggest that evolved retinal reduction in cave-dwelling Sinocyclocheilus occurs in a lens-independent fashion by the reduced proliferation and downregulation of transcriptional factors shown to have direct roles in retinal development and maintenance, including cone-rod homeobox (crx) and Wnt pathway members. These results show that the independent evolution of retinal degeneration in cavefish can occur by different developmental genetic mechanisms.

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“…Log 2 FC and P values were computed for each gene. If log 2 FC more than 1 and P value less than 0.05, genes were considered to be differentially expressed (Schartl et al 2012). …”

Section: Methodsmentioning

confidence: 99%

Evolution of the Eye Transcriptome under Constant Darkness in Sinocyclocheilus Cavefish

Meng¹,

Braasch²,

Phillips³

et al. 2013

Molecular Biology and Evolution

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“…Hence, the SLC45 family may represent an important target against cancer by limiting the energy access of tumour cells. Indeed, expression profiles link all four members of the SLC45 family to various cancer types (https://www.oncomine.org), including an up-regulation of SLC45A2 in melanoma and of SLC45A3 in prostate cancer [67,68]. Interestingly, up-regulation of SLC45A2 in eight of 11 melanoma cell lines was independent of melanization [68], suggesting an additional role to its involvement in producing protective pigmentation.…”

Section: A Role For the Slc45 Family In Cancer?mentioning

confidence: 99%

Proton-associated sucrose transport of mammalian solute carrier family 45: an analysis in Saccharomyces cerevisiae

Bartölke

Heinisch

Wieczorek

et al. 2014

Biochemical Journal

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The members of the solute carrier 45 (SLC45) family have been implicated in the regulation of glucose homoeostasis in the brain (SLC45A1), with skin and hair pigmentation (SLC45A2), and with prostate cancer and myelination (SLC45A3). However, apart from SLC45A1, a proton-associated glucose transporter, the function of these proteins is still largely unknown, although sequence similarities to plant sucrose transporters mark them as a putative sucrose transporter family. Heterologous expression of the three members SLC45A2, SLC45A3 and SLC45A4 in Saccharomyces cerevisiae confirmed that they are indeed sucrose transporters. [(14)C]Sucrose-uptake measurements revealed intermediate transport affinities with Km values of approximately 5 mM. Transport activities were best under slightly acidic conditions and were inhibited by the protonophore carbonyl cyanide m-chlorophenylhydrazone, demonstrating an H(+)-coupled transport mechanism. Na(+), on the other hand, had no effect on sucrose transport. Competitive inhibition assays indicated a possible transport also of glucose and fructose. Real-time PCR of mouse tissues confirmed mRNA expression of SLC45A2 in eyes and skin and of SLC45A3 primarily in the prostate, but also in other tissues, whereas SLC45A4 showed a predominantly ubiquitous expression. Altogether the results provide new insights into the physiological significance of SLC45 family members and challenge existing concepts of mammalian sugar transport, as they (i) transport a disaccharide, and (ii) perform secondary active transport in a proton-dependent manner.

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“…However, it is interesting how mitfa might become further up-regulated in Sp-Couch hybrids after UVB exposure, as well as the effects of UVB exposure on mitf target genes, such as dct , pmela , rab38a , tyr , tryp1a . It is noteworthy to mention that mitf levels are correlated with aggressive stage melanoma malignancy in the transgenic medaka- Xmrk melanoma model as well as human melanoma (Koludrovic et al, 2013; Schartl et al, 2010; Schartl et al, 2012). This may suggest that UVB serves to further up-regulate mitf and overwhelm normal cellular mechanisms (i.e., a single R/Diff gene copy) to keep xmrk in check and thereby initiating melanomagenesis.…”

Section: Resultsmentioning

confidence: 99%

“…The Gordon-Kosswig model led to the discovery of the xmrk oncogene, which is a mutant copy of the fish orthologue of the human Epidermal Growth Factor Receptor (EGFR; Weis and Schartl, 1998). Recently, the X. maculatus derive d xmrk oncogene, driven by the pigment cell specific mitf promoter, has been used to produce a transgenic medaka (Japanese rice fish, Oryzias latipes ) that develop aggressive melanoma within days of hatching with 100% penetrance (Schartl et al, 2010; Schartl et al, 2012). These transgenic Medaka models serve as experimentally tractable melanoma models and are currently being developed for small molecule screening regimen.…”

Section: Introductionmentioning

confidence: 99%

Molecular genetic response of Xiphophorus maculatus–X. couchianus interspecies hybrid skin to UVB exposure

Bowswell

et al. 2015

Comparative Biochemistry and Physiology Part C: Toxicology &

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The phenotypic and genetic similarities between Xiphophorus and human melanoma render Xiphophorus a useful animal model for studying the genetic basis of melanoma etiology. In the Xiphophorus model, melanoma has been shown to be inducible by ultraviolet light (UVB) exposure among interspecies hybrids, but not in parental line fish similarly treated. This leads to questions of what genes are responsive to UVB exposure in the skin of the interspecies hybrids, as well as how parental alleles in hybrids may be differentially regulated and the potential roles they may play in induced melanomagenesis. To address these questions, we produced X. maculatus Jp 163 B × X. couchianus (Sp-Couch) F1 hybrid fish, exposed both hybrid and parental fish to UVB, and performed gene expression profiling of the skin using RNA-Seq methodology. We characterized a group of unique UVB-responsive genes in Sp-Couch hybrid including dct, pmela, tyr, tyrp1a, slc2a11b, rab38a, rab27, tspan10, slc45a2, oca2, slc24a5, ptn and mitfa. These genes are associated with melanin production and melanocyte proliferation. They were also up-regulated in Sp-Couch hybrid, indicating their UVB response is hybridization initiated. In the hybrid, several melanin production and pigmentation related genes, including slc45a2, tspan10, dct, slc2a11b and ptn showed either X. couchianus or X. maculatus allele specific expression. The finding that these genes exhibit allele specific expression regulatory mechanisms in Sp-Couch hybrids, but do not exhibit a corresponding UVB response in either one of the parental fishes, may suggest UVB targets and imply mechanisms regarding the susceptibility of Sp-Couch to induced melanomagenesis.

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Conserved Expression Signatures between Medaka and Human Pigment Cell Tumors

Cited by 35 publications

References 46 publications

Evolution of the Eye Transcriptome under Constant Darkness in Sinocyclocheilus Cavefish

Evolution of the Eye Transcriptome under Constant Darkness in Sinocyclocheilus Cavefish

Proton-associated sucrose transport of mammalian solute carrier family 45: an analysis in Saccharomyces cerevisiae

Molecular genetic response of Xiphophorus maculatus–X. couchianus interspecies hybrid skin to UVB exposure

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