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Phosphatidylinositol 3-kinase signaling in mammalian preimplantation embryo development

C O'Neill, University of Sydney, Sydney, 2065, Australia

Correspondence: Chris O'Neill, Email: chriso{at}med.usyd.edu.au

Abstract

The development of the preimplantation mammalian embryo is an autopoietic process, once initiated development proceeds without an absolute requirement for external information or growth cues. This developmental autonomy is partly explained by the generation of autocrine trophic ligands, which are released and act back on the embryo via specific receptors. Several embryotrophic ligands cause receptor-dependent activation of 1-o-phosphatidylinositol 3-kinase. This enzyme phosphorylates phosphatidylinositol-4,5-bisphosphate to form phosphatidylinositol-3,4,5-trisphosphate. Genetic or pharmacological ablation of this enzyme activity disrupts normal development of preimplantation embryos. Phosphatidylinositol-3,4,5-trisphosphate is a membrane lipid that acts as a docking site for a wide range of proteins possessing the pleckstrin-homology domain. Such proteins are important regulators of cell survival, proliferation and differentiation. RAC-alpha serine/threonine-protein kinase is an important pleckstrin-homology domain protein and its activity is required for normal preimplantation embryo development and survival. The activity of a range of pleckstrin-homology domain proteins is also implicated in the normal development of the embryo. This review critically examines the evidence for the activation of 1-o-phosphatidylinositol 3-kinase in the generation of pleiotypic trophic response to embryotrophins in the autopoietic development of the preimplantation embryo.