Polarization of PI3K Activity Initiated by Ooplasmic Segregation Guides Nuclear Migration in the Mesendoderm

Asymmetric localization of RNA is a widely observed mechanism of cell polarization. Using embryos of the ascidian, Halocynthia roretzi, we previously showed that mesoderm and endoderm fates are separated by localization of mRNA encoding a transcription factor, Not, to the future mesoderm-side cytoplasm of the mesendoderm cell through asymmetric positioning of the nucleus. Here, we investigated the mechanism that defines the direction of the nuclear migration. We show that localization of PtdIns(3,4,5)P-3 to the future mesoderm region determines the direction of nuclear migration. Localization of PtdIns(3,4,5)P-3 was dependent on the localization of PI3K alpha to the future mesoderm region. PI3K alpha was first localized at the 1-cell stage by the ooplasmic movement. Activity of localized PI3K alpha at the 4-cell stage was required for the localization of PI3K alpha up to the nuclear migration. Our results provide the scaffold for understanding the chain of causality leading to the separation of germ layer fates.