Lluis Bassas

Developmental Regulation of Insulin and Type I Insulin-Like Growth Factor Receptors and Absence of Type II Receptors in Chicken Embryo Tissues

Chicken embryos are a suitable model for studying the role of insulin, insulin-like growth factors I and II (IGF-I and IGF-II), and their receptors in embryogenesis. We show that plasma membranes from heart, liver, and limb buds, as reported earlier for brain, each have a distinct developmental profile for insulin receptors and type I IGF receptors. In heart and limb buds, IGF binding is higher than insulin binding, but in liver, insulin receptors dominate. Expression of these receptors is, therefore, developmentally regulated and tissue specific. The wide distribution of high-affinity receptors capable of mediating insulin and IGF actions in early organogenesis further supports the possible importance of this family of peptides for differentiation and growth in vertebrates. In all chicken embryo tissues studied, both IGF-I and IGF-II appeared to bind to a type I IGF receptor. We have not detected a receptor with the peptide binding and structural characteristics of the mammalian type II IGF receptor. The type II receptor was absent in embryos, liver from newly hatched chicks, and adipocytes from older chicks, which suggests that the chicken may lack this subtype of IGF receptor.

Insulin and IGF receptors are developmentally regulated in the chick embryo eye lens

We have previously reported that insulin-like growth factor (IGF) receptors appear to predominate over insulin receptors in early stages of embryogenesis in the chick (days 2-3 whole embryo membranes). Overall, [125I]IGF I and II binding to specific receptors was maximal when the rate of brain growth is highest. In the present study we used the embryonic chick lens, a well-defined tissue composed of a single type of cell, to analyse whether changes of insulin and IGF I binding are correlated with changes in growth rate and differentiation state of the cells. We show that both insulin receptors and IGF receptors are present in the lens epithelial cells, and that each type is distinctly regulated throughout development. While there is a direct correlation between IGF-binding capability and growth rate of the cells, there is less relation to differentiation status and embryo age. Insulin receptors, by contrast, appear to be mostly related to the differentiated state of cells, decreasing sharply in fibers, irrespective of their developmental age.

Insulin receptors and insulin-like growth factor I receptors are functional during organogenesis of the lens

Insulin and insulin-like growth factor I (IGF-I) stimulate overall growth and development of the chick embryo in early organogenesis. Turning to individual organs, to clarify the cellular effects of these peptides and the activity of the receptors involved, we had demonstrated with developing lens that insulin and IGF-I increase the accumulation of delta-crystallin mRNA, a marker for lens differentiation, in part by stimulation of transcription. In this study we expand our previous work on lens receptors to an earlier time in organogenesis, day 4, which marks the beginning of differentiation of the lens epithelial cells into elongated fibers. Insulin receptors are demonstrable by affinity cross-linking in epithelial cells at day 6, and specific binding of [125I]insulin and [125I]IGF-I is detectable in day 4 lenses. Insulin and IGF-I stimulation of substrate phosphorylation in the presence of solubilized receptors occurs only with high concentrations (10-100 nM) of either peptide in day 4 lenses, while a clear response with low concentrations (1 nM) is elicited by day 6 of development. Low concentrations of both insulin and IGF-I (0.1-1 nM) increase the incorporation of [3H]leucine and [3H]uridine in day 6 lens cells, suggesting that each peptide acts through its own receptor. These results confirm and extend the finding of insulin and IGF-I receptors in the developing chicken lens, and demonstrate their functional activity. This embryonic model should be valuable for further analysis of the action of insulin and IGF-I in growth and differentiation processes during early development.

Chapter 5 Molecules of intercellular communication in vertebrates, invertebrates and microbes: do they share common origins?

Publisher Summary This chapter reviews (1) materials in microbes that resemble vertebrate receptors for hormones and other intercellular messengers, (2) intercellular communication in microbes, and (3) materials that resemble vertebrate hormones in microbes, higher plants, amphibian skin, and very young avian embryos. The term “glandulocentric” is introduced to indicate a traditional approach whereby each hormone is thought to be a unique product of one endocrine gland. Because the typical vertebrate endocrine gland is limited to vertebrates, its hormonal product had been thought to be similarly restricted in distribution. The one-to-one relationship between hormone and gland is similarly applied conceptually to the endocrine system in insects and in mollusks. Intercellular communication is widespread in microbes. In Saccharomyces cerevisiae, the common yeast, there are two sex types—α and A—which communicate one with the other via peptide messengers, designated α factor and A factor. Materials that resemble vertebrate-type messenger peptides are present in plants. The paleocentric approach, which suggests that these messengers originated early in evolution before the divergence of life forms into separate kingdoms, easily accommodates these observations. Many of the messenger peptides of vertebrate as well as their receptors and many of their post-receptor components have their evolutionary origins among the microbes and appear to be distributed among a very wide range of forms of life.

Insulin and insulin receptors in early chick embryo development

The physiological function of insulin in early embryonic life is unknown. Pancreatic insulin synthesis and secretion do not appear in chick embryos until 31/2 to 4 days of development. Nevertheless, immuno-active and bioactive insulin is present in eggs and in chick embryos at day 2 of development. Insulin receptors as well as insulin-like growth factor receptors are widespread in embryo tissues during the first week of embryogenesis. We suggest that endogenous insulin plays a physiological role in early embryo growth and differentiation even before emergence of the endocrine pancreas.