Extracellular signals are likely to be involved in the control of growth and differentiation during embryogenesis of vertebrates. These signals include, among others, several members of the insulin family: insulin-like growth factor (IGF)-I, IGF-II, and insulin. In the chick embryo, maternal IGF-I is stored in the yolk. In addition, the embryonic IGF-I gene is expressed very early and in late development in multiple tissues. We have used reverse-transcribed (RT) RNA and amplification by the polymerase chain reaction (PCR) to detect IGF-I gene expression. IGF-I was preferentially expressed in cephalic regions during late neurulation and early organogenesis. During late organogenesis, in some tissues, such as the eye lens, IGF-I gene expression is compartmentalized to a subset of cells, the epithelial cells. In these lens cells, IGF-I stimulates transcription of the delta-crystallin gene. Competence to respond to IGF-I exists in multiple cell types, since, based on binding studies, receptors for IGF-I are widespread in the gastrulating and neurulating embryo. Target tissues in which an autocrine/paracrine role for IGF-I appears more likely are the developing eye lens and retina, which are avascular organs rich in IGF-I receptors. In late development, IGF-I may have an additional endocrine role, with an impact on the general growth of the chick embryo. In embryos developed ex ovo, that show growth retardation after day 10 of embryogenesis, IGF-I serum levels are very low. By day 8, expression of IGF-I mRNA in these embryos is markedly reduced in multiple tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin-like growth factor-I (IGF-I) is the primary mediator of GH action after birth, but its role as a regulator of prenatal growth is unclear. In a previous study we showed that IGF-I mRNA was expressed in chicken embryos beginning at the blastoderm stage (day 0, newly laid egg). Here we present the ontogeny of serum IGF-I in normal and growth-retarded chicken embryos. Serum samples were pooled from multiple embryos starting on day 4 of development in ovo until hatching (day 21). Extracts of day 2 and 3 whole embryos were also studied. IGF-binding proteins were removed by filtration on Sep-Pak C-18 cartridges. IGF-I was quantitated by a heterologous RIA validated for chicken species. Embryonic IGF-I showed a HPLC profile similar to that of adult chicken serum IGF-I. Serum IGF-I was measurable on day 6 of development (approximately 0.04 ng/ml), reached a peak on day 15 (18 ng/ml), and decreased to a low concentration (0.2 ng/ml) the day before hatching. Embryos cultured ex ovo showed progressive growth retardation after day 10 of development, and by day 20 their weight was 50% of normal. The serum IGF-I concentration of ex ovo cultured embryos was normal on day 10, but remained low until day 21, without the midembryogenesis rise observed in normal embryos. These results support the concept that IGF-I may have a role in general embryonic growth in addition to any paracrine/autocrine action in individual tissues.

The avian embryo has been a useful model system for studies on the role of insulin and its close relative insulin-like growth factor-I (IGF-I) in development. The unfertilized chicken egg contains both peptides from maternal origin, and the embryo expresses insulin and IGF-I before the major organs are formed. Insulin receptors and IGF-I receptors are found in the blastoderm and in all tissues examined during organogenesis. When exogenous insulin or IGF-I are added to the embryo, growth and differentiation events are stimulated. By contrast, insulin antibodies and insulin receptor antibodies retard embryo development. In embryos cultured ex ovo, in which growth is impaired, the levels of serum IGF-I are decreased.