Phosphatidylinositol 3-Kinase Signaling Is Involved in Neurogenesis during Xenopus Embryonic Development

Ying Peng,Bing-Hua Jiang,Pai-Hao Yang,Zongxian Cao,Xianglin Shi,Marie C.M Lin,Ming-Liang He,Hsiang-Fu Kung

doi:10.1074/jbc.m402294200

Abstract

Phosphatidylinositol 3-kinase (PI3K) has numerous cellular functions, including cell survival and proliferation. In this study, we demonstrated that the expression of the active form of PI3K induced dorsal differentiation and axis duplication and strongly induced the expression of neural markers. In contrast, the inhibition of PI3K activity by its dominant negative mutant induced the phenotype of losing posterior structures and the expression of ventral markers. Akt is an essential target of PI3K for neurogenesis. The expression of the active form of Akt induced axis duplication and increased the expression of neural markers. Inhibition of the Akt activity abolished the PI3K-induced double heads and axes. This signal transmits through its target, glycogen synthase kinase 3beta, which is known to mediate Wnt signaling for Xenopus development. These results identify a new function of PI3K/Akt signaling in axis formation and neurogenesis during Xenopus embryonic development and provide a direct link between growth factor-mediated PI3K/Akt signaling and Wnt signaling during embryonic development.

Highlights

Phosphatidylinositol 3-kinase (PI3K) has numerous cellular functions, including cell survival and proliferation
Inhibition of the Akt activity abolished the PI3K-induced double heads and axes. This signal transmits through its target, glycogen synthase kinase 3␤, which is known to mediate Wnt signaling for Xenopus development. These results identify a new function of PI3K/Akt signaling in axis formation and neurogenesis during Xenopus embryonic development and provide a direct link between growth factor-mediated PI3K/Akt signaling and Wnt signaling during embryonic development
The embryos expressing p110␣* developed with double heads and dorsal axes (Fig. 1B). This result indicated that the activation of PI3K is sufficient to induce axis duplication and is a potent inducer for neurogenesis during Xenopus embryonic development

Summary

Introduction

Phosphatidylinositol 3-kinase (PI3K) has numerous cellular functions, including cell survival and proliferation. To study further the role of PI3K activity in neurogenesis, Xenopus embryos at the two-cell stage were injected with mRNAs coding for ␤-gal as a control or p110␣*. The co-expression of DN-Akt inhibited PI3K-induced axis duplication, resulting in a normal phenotype similar to that of the control (Fig. 3D).

Results

Conclusion