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Decreased expression but increased activity of PDK1 has been observed in neurodegenerative disease. To study  in vivo  function of PDK1 in neuron survival during cortical development, we generate forebrain-specific  PDK1  conditional knockout (cKO) mice. We demonstrate that  PDK1  cKO mice display striking neuron loss and increased apoptosis. We report that  PDK1  cKO mice exhibit deficits on several behavioral tasks. Moreover,  PDK1  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.

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