Expression of the IGFBP-2 gene in post-implantation rat embryos
Authors: Wood Teresa L. , Streck Randal D. , Pintar John E. 
Published: April 2021

The insulin-like growth factors (IGFs) stimulate ontogenesis in a variety of cell types both in vitro and in vivo. These effects are mediated by both IGF receptors and a family of IGF binding proteins (IGFBPs), which are found complexed with the IGFs in serum and tissue fluids. Here we compare the sites of expression during early rat embryogenesis of the genes encoding the RGD-containing IGF binding protein IGFBP-2 and IGF-H. At all ages from early post-implantation through midgestation, the expression of IGFBP-2 was highly complementary to IGF-H. IGFBP-2 mRNA was detected throughout the epiblast of the egg cylinder as early as e7, when IGF-H expression was restricted to trophectoderm and other extraembryonic cells. As gastrulation proceeded, IGFBP-2 expression ceased as IGF-H expression began in the newly formed embryonic and extra-embryonic mesoderm, but was retained in other epiblast derivatives including the surface ectoderm and neuroectoderm, throughout its rostral-caudal extent. By e10-ell, IGFBP-2 expression in neuroectoderm was restricted to the rostral brain of the primary neural tube and was found in the new population of neuroepithelium formed in the tail bud during secondary neurulation. IGFBP-2 expression remained high in the ventricular layer of the rostral brain into mid-gestation ages but decreased or disappeared as cells entered the mantle layer and began to express the neurofilament-related gene alpha-internexin. IGFBP-2 mRNA was abundant in surface ectoderm, particularly that of the branchial arches, and all ectodermal placodes. IGFBP-2 and IGF-H expression continued to be complementary throughout many non-neural tissues following gastrulation: IGFBP-2 was expressed at high levels in the surface ectoderm of the branchial arches while IGF-H was expressed at high levels in the mesenchyme of the branchial arches and at lower levels in the surface ectoderm; IGFBP-2 mRNA was prominent in the dorsal region of the developing foregut and throughout the hindgut; while IGF-H mRNA was prominent in cells of the ventral foregut but not detectable in the hindgut, and finally, IGFBP-2 mRNA was expressed in a restricted set of mesodermal tissues that did not express IGF-H including the notochord (especially when embedded in or adjacent to the dorsal gut), mesonephric tubules, and the anterior splanchnic mesodermal plate (ASMP) adjacent to the foregut. By el2 and through midgestation stages, IGFBP-2 expression was undetectable in the notochord and in caudal regions of the neural tube except for the floor plate, where expression was initiated at el3. The expression of IGFBP-2 either in populations of rapidly dividing cells (such as the epiblast and ventricular zone of rostral neuroepithelium) or in regions that direct the growth and differentiation of neighboring cells and tissues (including the surface ectoderm of the branchial arches, notochord, and the ASMP) suggests that IGFBP-2 may have important roles during development of numerous fetal tissues either by modulating IGF action or by acting independently of the IGFs as a constituent of the extracellular matrix.