The expression pattern of an insulin-like growth factor (IGF)-binding protein gene is distinct from IGF-II in the midgestational rat embryo

Abstract

Insulin-like growth factor-II (IGF-II), the predominant form of IGF in fetal and neonatal serum and tissues, is found in vivo complexed with IGF-binding proteins. One of these binding proteins, IGFBP-2, is present at high levels in fetal rat plasma and binds both IGF-I and IGF-II with high affinity. We here have used in situ hybridization to compare the distribution of IGFBP-2 mRNA with that of IGF-II mRNA in embryonic day 13.5-15 rat embryos. The spatial patterns of IGF-II and IGFBP-2 expression in the fetal trunk were distinct and, in general, nonoverlapping. Most mesoderm derivatives that express IGF-II at high levels contained little, if any, IGFBP-2 mRNA. Instead, IGFBP-2 mRNA was expressed at high levels in many cell types derived from ectoderm and endoderm. The expression of IGFBP-2 mRNA in the central nervous system (CNS) during this developmental period was examined in particular detail. The three most prominent sites of IGFBP-2 expression in the CNS were comprised of cells with nonneuronal phenotypes: 1) the epithelium of the choroid plexus, a tissue that produces cerebrospinal fluid; 2) the floor plate, an area that can guide axonal outgrowth from commissural neurons of the spinal cord in vitro; and 3) the infundibulum, the progenitor of the posterior pituitary that is believed to influence differentiation of the adjacent intermediate pituitary. In contrast, IGF-II mRNA was present at high levels in some cell types (e.g. the choroid mesenchyme and Rathke's pouch-derived progenitors of the anterior and intermediate pituitary lobes) immediately adjacent to cells expressing IGFBP-2, but was not detected near the floor plate. The distinct spatial expression patterns of the IGFBP-2 and IGF-II genes during midgestation suggest that the IGF-II-IGFBP-2 complex must, in many cases, form extracellularly after synthesis and secretion of the component molecules from distinct fetal cell populations. In addition, these results raise the possibility that IGFBP-2 may function not only in the transport of IGF-II, but also in other developmental processes that may be independent of IGF binding.