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Leiden, Netherlands

Schartl M.,University of Wurzburg | Kneitz S.,University of Wurzburg | Wilde B.,University of Wurzburg | Wagner T.,University of Wurzburg | And 3 more authors.
PLoS ONE | Year: 2012

Aberrations in gene expression are a hallmark of cancer cells. Differential tumor-specific transcript levels of single genes or whole sets of genes may be critical for the neoplastic phenotype and important for therapeutic considerations or useful as biomarkers. As an approach to filter out such relevant expression differences from the plethora of changes noted in global expression profiling studies, we searched for changes of gene expression levels that are conserved. Transcriptomes from massive parallel sequencing of different types of melanoma from medaka were generated and compared to microarray datasets from zebrafish and human melanoma. This revealed molecular conservation at various levels between fish models and human tumors providing a useful strategy for identifying expression signatures strongly associated with disease phenotypes and uncovering new melanoma molecules. © 2012 Schartl et al.

Jimenez-Amilburu V.,Max Planck Institute for Heart and Lung Research | Jong-Raadsen S.,ZF screens BV | Bakkers J.,University Utrecht | Spaink H.P.,Leiden University | Marin-Juez R.,ZF screens BV
Journal of Endocrinology | Year: 2015

Cardiomyopathies-associated metabolic pathologies (e.g., type 2 diabetes and insulin resistance) are a leading cause of mortality. It is known that the association between these pathologies works in both directions, for which heart failure can lead to metabolic derangements such as insulin resistance. This intricate crosstalk exemplifies the importance of a fine coordination between one of the most energy-demanding organs and an equilibrated carbohydrate metabolism. In this light, to assist in the understanding of the role of insulinregulated glucose transporters (GLUTs) and the development of cardiomyopathies, we have developed a model for glut12 deficiency in zebrafish. GLUT12 is a novel insulin-regulated GLUT expressed in the main insulin-sensitive tissues, such as cardiac muscle, skeletal muscle, and adipose tissue. In this study, we show that glut12 knockdown impacts the development of the embryonic heart resulting in abnormal valve formation. Moreover, glut12-deficient embryos also exhibited poor glycemic control. Glucose measurements showed that these larvae were hyperglycemic and resistant to insulin administration. Transcriptome analysis demonstrated that a number of genes known to be important in cardiac development and function as well as metabolic mediators were dysregulated in these larvae. These results indicate that glut12 is an essential GLUT in the heart where the reduction in glucose uptake due to glut12 deficiency leads to heart failure presumably due to the lack of glucose as energy substrate. In addition, the diabetic phenotype displayed by these larvae after glut12 abrogation highlights the importance of this GLUT during early developmental stages. © 2015 Society for Endocrinology.

Yang S.,Leiden University | Marin-Juez R.,ZF screens BV | Marin-Juez R.,Max Planck Institute for Heart and Lung Research | Meijer A.H.,Leiden University | Spaink H.P.,Leiden University
BMC Genomics | Year: 2015

Background: Although the responses to many pathogen associated molecular patterns (PAMPs) in cell cultures and extracted organs are well characterized, there is little known of transcriptome responses to PAMPs in whole organisms. To characterize this in detail, we have performed RNAseq analysis of responses of zebrafish embryos to injection of PAMPs in the caudal vein at one hour after exposure. We have compared two ligands that in mammals have been shown to specifically activate the TLR2 and TLR5 receptors: Pam3CSK4 and flagellin, respectively. Results: We identified a group of 80 common genes that respond with high stringency selection to stimulations with both PAMPs, which included several well-known immune marker genes such as il1b and tnfa. Surprisingly, we also identified sets of 48 and 42 genes that specifically respond to either Pam3CSK4 or flagellin, respectively, after a comparative filtering approach. Remarkably, in the Pam3CSK4 specific set, there was a set of transcription factors with more than 2 fold-change, as confirmed by qPCR analyses, including cebpb, fosb, nr4a1 and egr3. We also showed that the regulation of the Pam3CSK4 and flagellin specifically responding sets is inhibited by knockdown of tlr2 or tlr5, respectively. Conclusions: Our studies show that Pam3CSK4 and flagellin can stimulate the Tlr2 and Tlr5 signaling pathways leading to common and specific responses in the zebrafish embryo system. © 2015 Yang et al.

Marin-Juez R.,University of Barcelona | Marin-Juez R.,ZF screens BV | Rovira M.,University of Barcelona | Crespo D.,University of Barcelona | And 4 more authors.
Journal of Cerebral Blood Flow and Metabolism | Year: 2015

Glucose transporter 2 (GLUT2; gene name SLC2A2) has a key role in the regulation of glucose dynamics in organs central to metabolism. Although GLUT2 has been studied in the context of its participation in peripheral and central glucose sensing, its role in the brain is not well understood. To decipher the role of GLUT2 in brain development, we knocked down slc2a2 (glut2), the functional ortholog of human GLUT2, in zebrafish. Abrogation of glut2 led to defective brain organogenesis, reduced glucose uptake and increased programmed cell death in the brain. Coinciding with the observed localization of glut2 expression in the zebrafish hindbrain, glut2 deficiency affected the development of neural progenitor cells expressing the proneural genes atoh1b and ptf1a but not those expressing neurod. Specificity of the morphant phenotype was demonstrated by the restoration of brain organogenesis, whole-embryo glucose uptake, brain apoptosis, and expression of proneural markers in rescue experiments. These results indicate that glut2 has an essential role during brain development by facilitating the uptake and availability of glucose and support the involvement of glut2 in brain glucose sensing. © 2015 ISCBFM. All rights reserved.

Minegishi Y.,Leiden University | Henkel C.V.,ZF screens BV | Dirks R.P.,ZF screens BV | van den Thillart G.E.E.J.M.,Leiden University
Marine Biotechnology | Year: 2012

Freshwater eels (genus Anguilla), especially the species inhabiting the temperate areas such as the European, American and Japanese eels, are important aquaculture species. Although artificial reproduction has been attempted since the 1930s and large numbers of studies have been conducted, it has not yet fully succeeded. Problems in eel artificial breeding are highly diverse, for instance, lack of basic information about reproduction in nature, no appropriate food for larvae, high mortality, and high individual variation in adults in response to maturation induction. Over the last decade, genomic data have been obtained for a variety of aquatic organisms. Recent technological advances in sequencing and computation now enable the accumulation of genomic information even for non-model species. The draft genome of the European eel Anguilla anguilla has been recently determined using Illumina technology and transcriptomic data based on next generation sequencing have been emerging. Extensive genomic information will facilitate many aspects of the artificial reproduction of eels. Here, we review the progress in genome-wide studies of eels, including additional analysis of the European eel genome data, and discuss future directions and implications of genomic data for aquaculture. © 2012 The Author(s).

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