Abstract
Insulin-like growth factors (IGFs) are evolutionarily conserved peptides that are essential for normal animal growth and development. Recent studies utilizing cell cultures suggest that the bioactivity of IGFs could be modulated by several high-affinity IGF-binding proteins (IGFBPs). The in vivo roles of these IGFBPs, however, are poorly defined. Research in this area has relied heavily on rodent models, and attempts have been hampered by the inaccessibility of the mammalian fetus which is enclosed in the uterus. We have been using a model teleost fish, the zebrafish, to investigate the role of IGFBPs in specifying the IGF actions in vivo. To date, cDNAs encoding several IGFBPs have been cloned and characterized from zebrafish, and their spatial and temporal expression profiles mapped. The results indicated that the structure and expression patterns of these molecules are highly conserved in fish. In cultured zebrafish cells, both IGFBP-1 and -2 act as inhibitors of IGF actions. To determine how IGFBP functions in vivo, IGFBP-2 was targeted expressed in the zebrafish embryos. Using these transgenic fish, the actions of IGFBP-2 in specifying IGF actions were investigated, and the results indicated that IGFBP-2 can inhibit fish growth in a liganddependent manner.
