Insulin-like growth factor II acts through an endogenous growth pathway regulated by imprinting in early mouse embryos.

Abstract

We present evidence that insulin-like growth factor II (IGF-II) mediates growth in early mouse embryos and forms a pathway in which imprinted genes influence development during preimplantation stages, mRNA and protein for IGF-II were expressed in preimplantation mouse embryos, but the related factors IGF-I and insulin were not. IGF-I and insulin receptors and the IGF-II/mannose-6-phosphate receptor were expressed. Exogenous IGF-II or IGF-I increased the cell number in cultured blastocysts, but a mutant form of IGF-II that strongly binds only the IGF-II receptor did not. Reduction of IGF-II expression by antisense IGF-II oligonucleotides decreased the rate of progression to the blastocyst stage and decreased the cell number in blastocysts. Preimplantation parthenogenetic mouse embryos expressed mRNA for the IGF-II receptor but not for either IGF-II ligand or the IGF-I receptor, indicating that the latter genes are not expressed when inherited maternally. These data imply that some growth factors and receptors, regulated by genomic imprinting, may control cell proliferation from the earliest stages of embryonic development.

Transcriptome Expression Profiles in Prenatal Pigs in Relation to Myogenesis

“…While the IGF proteins are also potent prenatal activators, it is mainly the IGF-II that acts prenatal (Rappolee et al, 1992;Stylianopoulou et al, 1988). However, neither IGF-I nor IGF-II, nor the receptors were greatly differentially regulated.…”

Activities of growth factors in preimplantation embryos

“…The relevant ligand in mouse could be embryo-derived TGFa since the corresponding mRNA (like the EGFreceptor mRNA) is found in increasing concentrations which reach high levels at the blastocyst stage. The TGFa protein is also detectable by the blastocyst stage [Rappolee et al, 19881 and is located mainly on the ICM and polar trophectoderm cells [Dardik et al, 19921. Since the ligand can create a developmental signal only after binding to the EGF-receptor, various assays have been used t o demonstrate the occurrence of the receptor on the surface of embryo cells ( Wiley et al, Wiley et al, 1992Dardik et al, 1992Mattson et al, 1988Heyner et al, 1989 Rosenblum et al, 1986 Harvey and Kaye, 1991h Rappolee et al, 1990Rappolee et al, , 1992 Rappolee et al, 1990 Rappolee et al, 1990Rappolee et al, , 1992 Schultz et al, 1993Schultz et al, 1993Palmieri et al, 1992a Paria et al, 1992…”

“…Several types of growth factors can influence preimplantation development in vitro, but this merely illustrates the presence of an active receptor rather than the necessity for the growth factor for development. Cytokines are involved in the latter stages of the pre-or peri-implantation embryo as the embryo meets the challenge of the mother's Rappolee et al, 1988Rappolee et al, 1988Dardik et al, 1992Rappolee et al, 1988Rappolee et al, 1988Rappolee et al, 1988Rappolee et al, 1990Rappolee et al, 1990Rizzino, 1985Rappolee et al, 1990Rappolee et al, 1990Rappolee et al, 1990Rappolee et al, 1992Rappolee et al, 1988Rappolee et al, 1988Paria et al, 1992Palmieri et al, 1992aPalmieri et al, 1992aPalmieri et al, 1992a Murray et al, Murray et al, 1990 immune system. Studies such as these are the focus of this essay.…”

“…We speculate that when the receptors start to receive signals from endogenous TGFa they shift to an internal location. It Harvey and Kaye, 1990Kaye, , 1991a Gardner and Kaye, 1991 Rao et al, 1990Harvey and Kaye, 1991aRappolee et al, 1992 Harvey and Kaye, 1992b.…”

The expression of the imprinted genes H19 and IGF-2 in choriocarcinoma cell lines. Is H19 a tumor suppressor gene?

“…The tissue-speci®c expression pattern of IGF-2 is very similar to that of the H19 gene (Rappolee et al, 1992;Goshen et al, 1993) and, its expression is also postnatally depressed in many adult tissues (Rechler and Nissley, 1990). Prominent exceptions are the adult liver and the choroid plexus which continue to express IGF-2 at relatively high levels postnatally.…”