ROYER, T; MAURES, T; DUAN, C: Spatial and temporal expression profiles of IGF ligands, receptors, and binding proteins in developing zebrafish embryos

To better understand how various components of the insulin-like growth factor (IGF) signaling system regulate embryonic tissue formation and growth in a teleost model organism, the zebrafish, we mapped the spatio-temporal expression patterns of IGF-I, IGF-II, two IGF-IRs, and several IGFBPs in developing zebrafish embryos by RT-PCR and whole mount in situ hybridization. Transcripts for IGF-I and -II mRNAs were found throughout embryogenesis and were distributed in a ubiquitous manner throughout embryogenesis. After hatching, however, the expression of IGF-II mRNA, but not IGF-I, was restricted to the anterior portion of the body, most obviously in the eyes, brain, and other nervous tissues. In contrast to the presence of a single IGF-IR gene in mammals, two distinct IGF-IR genes, termed igf-1ra and igf-1rb, were found in zebrafish. Like their ligands, the IGF-IRa and IGF-IRb transcripts were observed in all the cells throughout early stages. The relative level of IGF-IRa mRNA was low during early embryogenesis and increased in the hatched larva whereas the situation was reversed for IGF-IRb mRNA. In contrast to the ubiquitous presence of IGF ligands and receptors, the individual IGFBPs were found to be expressed in a highly tissue-specific and developmentally regulated manner. For instance, the levels of IGFBP-1 mRNA in early embryos were very low, but became highly expressed in the liver after hatching. Likewise, IGFBP-2 mRNA was only detected in the retina and a subset of neurons in the developing brain. These expression patterns suggest that the availability of IGFs to various embryonic tissues may be regulated by specific IGFBPs expressed locally, and that this regulation may be crucial for embryonic tissue formation and growth (Supported by NSF IBN-9728911 and IBN-0110864).