THE AVIAN IGF TYPE-1 RECEPTOR - CDNA ANALYSIS AND IN-SITU HYBRIDIZATION REVEAL CONSERVED SEQUENCE ELEMENTS AND EXPRESSION PATTERNS RELEVANTFOR THE DEVELOPMENT OF THE NERVOUS-SYSTEM

Insulin-like growth factor type 1 receptor (IGF-1R) is a tyrosine kina se with a key role in development. The primary structure of IGF-1R is known for mammalian species, but not for birds. The avian embryo, howe ver, provides an ideal system for the experimental study of neurogenes is. We therefore cloned the complete coding sequence of the chicken IG F-1R from a cDNA library and analyzed its embryonic expression by Nort hern blot and in situ hybridization. The deduced chicken IGF-1R precur sor of 1363 amino acids was 85% identical to human IGF-1R and did not show deletions or insertions in critical positions, when compared to i ts mammalian homologues. Notably, all cysteine residues in the extrace llular domains, and 15 of the 17 N-linked glycosylation sites found in human IGF-1R were also present in the chicken receptor. An 11 kb tran script was abundant in developing nervous tissues, kidney, pancreas an d the gastrointestinal tract. The early in situ expression patterns in 20-somite embryos revealed high levels of IGF-1R mRNA in the neuroepi thelia, notochord and somites. At embryonic day 4 (E4), high concentra tions of IGF-1R transcripts were found again primarily in the neuroepi thelia and, to a lesser degree, in the sensory ganglia and diverse mes enchymal derivatives. During the second half of embryonic development, IGF-1R expression in the CNS was particularly abundant in telencephal ic regions, including the olfactory bulb, hippocampus, striatum and pi riform cortex, and also in the optic tectum and cerebellum. By the use of cDNA cloning and in situ hybridization this study reveals conserve d amino acid sequence elements between birds and mammals, and developm ental expression patterns that an compatible with an important role of this receptor in growth, differentiation and maturation of the avian CNS.