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Somatostatin is a neuropeptide and a key regulator of the growth axis. Six Sst encoding genes (sst1 to sst6) have been identified in teleost fish genomes but little is known about their function. The present study aimed at replicating the context of the inflammatory bowel disease (IBD) and clarifying the involvement of sst3 in the intestine innate defence barrier in zebrafish larvae. We first established a CRISP/Cas9 sst3 deficient line (MT) and analysed the morphological and transcriptomic response to 0.4% dextran sulfate sodium (DSS). Alcian blue staining of larval sections 6 days post fertilization showed an increased in acidic mucins in the intestinal bulb and mid-intestine, with a much stronger response in the MT compared to wild type (WT). The transcriptomic analysis revealed that WT and MT shared enriched gene ontology (GO) terms and pathways linked to catabolism, chondrocyte development, innate immune system, xenobiotic metabolism and oxidative stress. In contrast, the WT specific response to DSS was enriched in GO terms and pathways linked to transcription and translation, various developmental processes, regulation of biosynthetic processes, apelin signalling and apoptosis while the MT specific response included terms and pathways linked to protein metabolism and catabolic processes, extracellular matrix – receptor interaction and proteasome and chondrocyte development. Overall, this study demonstrated that Sst3 deficiency impairs insulin growth factor and adipocytokine signalling exacerbating the inflammatory response to DSS.

Somatostatin (SST) plays important roles in growth and development. In teleost fishes six SST encoding genes (sst1 to sst6) have been identified although few studies have addressed their function. Here we aim to determine the function of the teleost specific sst4 in the zebrafish. A CRISPR/Cas9 sst4 zebrafish mutant with loss of function (sst4−/−) was produced which grew significantly faster and was heavier at the onset of gonadal maturation than the wild type (WT). Consistent with their faster growth, liver igf1, igf2a and igf2b expression was significantly upregulated in the sst4−/− fish compared to the WT. Histological examination of the ovaries and testis indicated that sst4−/− fish had slightly delayed testicular gametogenesis compared to the WT. Significantly lower expression of igf3, amh, insl3, hsd17b3, hsd11b2, hsd20b, cyp11b and cyp17 was consistently observed in the sst4−/− testis. In contrast, the ovaries had lower expression of igf1, igf2a and cyp19a1a but increased expression of igf2b and hsd20b. The gonadotrophin beta subunits (fshb and lhb) in the brain were downregulated indicating the brain-pituitary-gonadal axis was downregulated in the sst4−/− fish and suggesting that the steroid production is compromised in the maturing gonads. In addition, analysis of sst1 and sst3 mRNA levels in sst4−/− fish suggests a dosage compensation effect of sst1 in the brain and liver. Altogether, the results from the zebrafish sst4−/− line support the idea that sst4 is involved in the regulation of igf signalling, somatic growth and reproduction since steroidogenesis and gametogenesis at pubertal onset were compromised. Keywords: Somatostatin 4, Gametogenesis, Zebrafish, Gonadotrophin, Puberty

One of the goals of the aquaculture industry is to understand and control growth associated traits through selective breeding. In the present study the molecular basis of growth heterogeneity in the European sea bass (Dicentrarchus labrax) was addressed. To establish growth heterogeneity in a group of hatchery bred sea bass individuals were tagged and their specific growth rates (SGR) determined at monthly intervals. Gene expression in the brain, liver and white muscle from fish with the most divergent sustained SGR (6 individuals of the first and last quartile) was assessed using SuperSAGE (Serial Analysis Gene Expression) combined with next generation SOLiD4 sequencing. A total of approx. 11 million edited tags (26 bp), on average 2 million tags per SAGE library, that represented 47.071 unique transcripts were identified. Comparison of transcripts in fish with high and low SGR yielded 344, 698 and 601 differently expressed tags (0.01% false discovery rate and 4-fold change) in brain, liver and muscle, respectively. The tags were mapped onto the sea bass genome and approximately one third of the tags could be assigned to annotated genes. Pathway enrichment analysis revealed in liver, muscle and brain intricate gene expression changes in endocrine regulatory pathways involved in growth, metabolic and the stress axis, underlying divergent SGR in sea bass. Keywords: European sea bass, Specific growth rate, Gene expression, SuperSAGE, Pathways