A zebrafish view of the insulin-like growth factor signaling pathway

Insulin like growth factors (IGFs), including IGF-` and IGF-a, are evolutionarily conserved peptides that are essential for vertebrate growth and development. The biological actions of IGFs are mediated through the IGF-` receptor, a receptor tyrosine kinase. Recent studies utilizing cell cultures suggest that the bioactivity of IGFs could also be modulated by several high affinity IGF binding proteins (IGFBPs). The developmental roles of various members of the IGF signaling pathway, however, are not well underatood. 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. In recent years, there has been a remarkable acceleration in our understanding of the IGF signaling system in a model teleost fish, the zebrafish. To date, cDNAs encoding zebrafish IGF-`, IGF-a, IGF-` receptors(IGF-`Rs), and several IGFBPs have been cloned and characterized, and their spatial and temporal expression patterns determined using the transparent zebrafish embryos. Using cultured cells and transgenic fish, the actions of IGFs, IGF-`Rs and IGFBPs in regulating cell proliferation, differentiation, and apoptosis during early development have been studied. This review will focus on our current understanding of the structure, gene expression, physiological regulation, and biological actions of IGF ligands, receptors, and IGFBPs in zebrafish. The unique value of the free-living and transparent zebrafish embryos for growth physiology will also be discussed ;Acta Zoologica Sinica 49(4):421-431,2003