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E-GEOD-42070 - Proprotein Convertase Subtilisin/Kexin Type 7 (PCSK7) Is Essential for the Zebrafish Development and Bioavailability of Transforming Growth Factor β1a (TGFβ1a)

Status
Released on 2 January 2014, last updated on 2 June 2014
Organism
Danio rerio
Samples (12)
Array (1)
Protocols (7)
Description
Proprotein convertase subtilisin/kexin (PCSK) enzymes convert proproteins into bioactive end products. Although other PCSK enzymes are known to be essential for biological processes ranging from cholesterol metabolism to host defense, the in vivo importance of the evolutionarily ancient PCSK7 has remained enigmatic. Here, we quantified the expressions of all pcsk genes during the 1st week of fish development and in several tissues. pcsk7 expression was ubiquitous and evident already during the early development. To compare mammalian and zebrafish PCSK7, we prepared homology models, which demonstrated remarkable structural conservation. When the PCSK7 function in developing larvae was inhibited, we found that PCSK7-deficient fish have defects in various organs, including the brain, eye, and otic vesicle, and these result in mortality within 7 days postfertilization. A genome-wide analysis of PCSK7-dependent gene expression showed that, in addition to developmental processes, several immune system-related pathways are also regulated by PCSK7. Specifically, the PCSK7 contributed to the mRNA expression and proteolytic cleavage of the cytokine TGFβ1a. Consequently, tgfβ1a morphant fish displayed phenotypical similarities with pcsk7 morphants, underscoring the importance of this cytokine in the zebrafish development. Targeting PCSK activity has emerged as a strategy for treating human diseases. Our results suggest that inhibiting PCSK7 might interfere with normal vertebrate development. Gene expressions of zebrafish were measured at 6 and 24 hours post fertilization of the fish samples with PCSK7 blocked with morpholino technology. For each time point, triplicate samples pooled from 18-35 zebrafish embryos were used. Also gene expressions from triplicate control samples were measured.
Experiment type
transcription profiling by array 
Contacts
Anna Oksanen, Annemari Uusimäki, Hannu Turpeinen, Marko Pesu, Mataleena Parikka, Matti Nykter, Mika Rämet, Sampo Kukkurainen, Vesa Hytönen, Virpi Kivinen
Citation
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-42070.idf.txt
Sample and data relationshipE-GEOD-42070.sdrf.txt
Raw data (1)E-GEOD-42070.raw.1.zip
Processed data (1)E-GEOD-42070.processed.1.zip
Array designA-GEOD-14664.adf.txt
Links