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)P3 to the future mesoderm region determines the direction of nuclear migration. Localization of PtdIns(3,4,5)P3 was dependent on the localization of PI3Kα to the future mesoderm region. PI3Kα was first localized at the 1-cell stage by the ooplasmic movement. Activity of localized PI3Kα at the 4-cell stage was required for the localization of PI3Kα up to the nuclear migration. Our results provide the scaffold for understanding the chain of causality leading to the separation of germ layer fates. [Display omitted] •Germ layer fates are separated by nuclear migration toward localized PtdIns(3,4,5)P3•PtdIns(3,4,5)P3 is localized to the mesoderm region through localization of PI3Kα•Maternal PI3Kα activity at the 4-cell stage localizes PI3Kα during later stages•Re-localization of maternal PI3Kα is important for nuclear migration Takatori et al. show that the destination of nuclear migration within the mesendoderm cell, which defines the future mesoderm region in the ascidian embryo, is determined by localization of PI3K, first created by ooplasmic movement following fertilization and maintained using localized PI3K activity.