PDK1 Plays An Important Role In The Development Of Dentate Gyrus

Hippocampus is a crucial cortical region and administers learning and memory.Dentate gyrus is the first gateway receiving afferent imput from the Entorhinal Cortex.The signal comes out from dentate gyrus to the CA zones then comes back to dentate gyrus which constitutes the classic circuit to form memories.Its substructure SGZ(subgranular zone)harbors the Tbr2 positive neuronal progenitors which can generate neurons throughout adulthood when occurs to enriched environment,stress and so on.Moreover these new born neurons can integrate into the existed neural circuit then perform the normal function.3-phosphoinositide-dependent protein kinase-1(PDK1)is a regulator of AGC kinases compromised with PKA? AKT(PKB)?S6K?SGK and PKC.PDK1 phosphorylates the highly conserved sequences on their T-loops by which to activate these protein kinases.These downstreams are associated with cell apoptosis?survival?glucose uptake and storage and so on in mammals.There is no much research focused on the function of PDK1 in nervous system.Just a few papers reported that ablation of PDK1 in nestin+ cells would result in the microcephaly.To learn more about the function of PDK1 in brain we used the Cre-Loxp approach to knock out PDK1 in Emx1 positive cells conditionally which are expressed in the dorsal telencephalon.We find the mutant mice have weaker capacity of learning and memory associated with hippocampus.Through morphology approaches the mutant postnatal hippocampus is found to have a smaller size than control.DG is the most severely impacted substructure with abnormal appearance more than decreased cell numbers.We use immunohistochemical method to detect the function of PDK1before birth and find the ablation of PDK1 impacts the development of DG via reducing proliferation?increasing differentiation and hypogenetic radial glial scaffold.PDK1 could phosphorylate the Thr308 site of AKT whose Ser473 is phosphorylated by m TOR2.AKT is proved to be related with the survival and proliferation of neurons and m TORC2 is found to participate in the formation of dendritic of neurons.It is significant that if PDK1 modulate the development of DG via controlling these two signals.