Old hormones of the insulin family as new developmental signals

Abstract

Insulin was first identified as an anabolic pancreatic hormone responsible for glucose homeostasis, and Insulin-like Growth Factor (IGF-I) as the mediator of the action of Growth Hormone on postnatal growth. New molecular, pharmacological and embryological information has broadened the scope of the physiological roles of these hormones and their related molecules, particularly the insulin precursor proinsulin, during vertebrate development. Studies in our laboratory have demonstrated that proinsulin is expressed and functional before emergence of the pancreas. Proinsulin gene expression in the chick and mouse embryo shows fine transcriptional and postrancriptional regulation with generation of specific embryonic transcripts which are differentially translated. The protein product remains as unprocessed proinsulin that protects the cells from excessive apoptosis during neurulation. In contrast, IGF-I is expressed later than proinsulin in the chick embryo and it starts in the nervous system. In the mouse embryo, generation of olfactory bulb stem cells in culture has allowed the study of these molecules' role in the proliferation and differentiation of neural precursors. Proinsulin and IGF-I can cooperate with mitogens (EGF and FGF2) in the control of stem/ precursor cells proliferation and IGF-I is an essential factor for neural differentiation. Mice deficient in IGF-I present a disruption of olfactory bulb cytoarchitecture, with decreased numbers of mitral cells and abnormal radial glia. This article gives thus an overview of the important role of insulin family proteins in development.