Conditional Deletion of PDK1 in the Forebrain Causes Neuron Loss and Increased Apoptosis during Cortical Development

Abstract

Decreased expression but increased activity of PDK1 has been observed in neurodegenerative disease. To study <i>in vivo</i> function of PDK1 in neuron survival during cortical development, we generate forebrain-specific <i>PDK1</i> conditional knockout (cKO) mice. We demonstrate that <i>PDK1</i> cKO mice display striking neuron loss and increased apoptosis. We report that <i>PDK1</i> cKO mice exhibit deficits on several behavioral tasks. Moreover, <i>PDK1</i> cKO mice show decreased activities for Akt and mTOR. These results highlight an essential role of endogenous PDK1 in the maintenance of neuronal survival during cortical development.