Structure, Developmental Expression, and Physiological Regulation of Zebrafish IGF Binding Protein-1

The biological activity and availability of IGFs are regulated by a group of secreted proteins that belong to the IGF-binding protein (IGFBP) gene family. Although six IGFBPs have been identified and studied in mammals, their nonmammalian orthologs remain poorly defined. In this study, we cloned and characterized the full-length zebrafish IGFBP-1. Sequence analysis indicated that its structure is homologous to mammalian IGFBP-1. Using in situ RNA hybridization and RT-PCR, we discovered that IGFBP-1 mRNA was present in all early embryonic stages albeit at very low levels. IGFBP-1 mRNA was initially expressed in multiple embryonic tissues but became restricted to the liver shortly after hatching. In the adult stage, IGFBP-1 mRNA was found only in the liver at low levels. Prolonged food deprivation caused a significant increase in the hepatic IGFBP-1 mRNA levels, and refeeding restored the IGFBP-1 mRNA to the basal levels. When adult fish or embryos were subjected to hypoxic conditions, the IGFBP-1 mRNA expression increased dramatically. Intriguingly, the hypoxia-induced IGFBP-1 expression operated in different embryonic tissues in a developmental-stage-dependent manner. In early embryos, hypoxia-stimulated IGFBP-1 mRNA expression in the pharyngeal arches, ventricle, atrium, and brain. After hatching, the hypoxia-induced IGFBP-1 expression became liver specific. These results not only provide new information about the structural conservation, developmental expression, and physiological regulation of the IGFBP-1 gene but also present the opportunity to elucidate the developmental role of IGFBP-1 using a unique vertebrate model organism.