Insulin-like growth factor II acts through an endogenous growth pathway regulated by imprinting in early mouse embryos.
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.
Rappolee
D A
DA
Department of Anatomy, University of California, San Francisco 94143-0750.
Sturm
K S
KS
Behrendtsen
O
O
Schultz
G A
GA
Pedersen
R A
RA
Werb
Z
Z
D000818:Animals; D001755:Blastocyst / Q000378:metabolism*; D005314:Embryonic and Fetal Development / Q000235:genetics; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000235:genetics; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011972:Receptor, Insulin / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D017451:Receptors, Somatomedin; D014158:Transcription, Genetic / Q000235:genetics
D016376:Oligonucleotides, Antisense; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin