Selective induction of neocortical GABAergic neurons by the PDK1-Akt pathway through activation of Mash1

Oishi, Koji; Watatani, Kenji; Itoh, Yoshio; Okano, Hideyuki; Guillemot, François; Nakajima, Kazunori; Gotoh, Yukiko

doi:10.1073/pnas.0808400106

Cited by 68 publications

(66 citation statements)

References 48 publications

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“…investigations showing that inhibition of 3-phosphoinositide-dependent protein kinase 1/Akt signaling reduces neurogenesis in neural progenitor cells, whereas constitutive activation of Akt or phosphatase and tensin homolog deletion promotes neurogenesis (Oishi et al, 2009;Gregorian et al, 2009). These results support the argument that FoxO negatively regulates neurogenesis in the brain.…”

Section: Foxos Play a Inhibitory Role In Neurogenesis And Synaptogenesissupporting

confidence: 78%

Forkhead box O transcription factors as possible mediators in the development of major depression

et al. 2015

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Section: Foxos Play a Inhibitory Role In Neurogenesis And Synaptogenesissupporting

confidence: 78%

Forkhead box O transcription factors as possible mediators in the development of major depression

et al. 2015

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“…To examine the role of PDK1 in neocortical development, we first crossed mice harboring a floxed Pdpk1 allele (23) with those harboring a transgene for Cre recombinase under the control of a Nestin enhancer (24) to delete Pdpk1 in neural progenitor cells (NPCs) and their descendants throughout the CNS. We previously showed that PDK1 flox/flox ;Nestin-Cre mice die shortly after birth and have a reduced brain size (25). Immunohistofluorescence and immunoblot analyses confirmed that the abundance of PDK1 protein as well as the extent of Akt activation (as reflected by PDK1-mediated phosphorylation of Akt at Thr 308 or phosphorylation of Akt substrates with a typical Akt phosphorylation consensus sequence) were markedly reduced in the brains of such mice at postnatal day (P) 0 (Fig.…”

Section: Resultsmentioning

confidence: 74%

“…The PDK1-Akt pathway contributes to the regulation of proliferation, survival, differentiation of, and metabolism in various cell types (22,25,36), but its role in neuronal migration has been unclear. We demonstrated a role for the PDK1-Akt pathway in neocortical neurons through the specific manipulation of postmitotic cells with the use of Nex Cre/+ mice or a Neurod1 promoterdependent Cre expression plasmid.…”

Section: Discussionmentioning

confidence: 99%

PDK1–Akt pathway regulates radial neuronal migration and microtubules in the developing mouse neocortex

Itoh

Higuchi

Oishi

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Neurons migrate a long radial distance by a process known as locomotion in the developing mammalian neocortex. During locomotion, immature neurons undergo saltatory movement along radial glia fibers. The molecular mechanisms that regulate the speed of locomotion are largely unknown. We now show that the serine/threonine kinase Akt and its activator phosphoinositide-dependent protein kinase 1 (PDK1) regulate the speed of locomotion of mouse neocortical neurons through the cortical plate. Inactivation of the PDK1–Akt pathway impaired the coordinated movement of the nucleus and centrosome, a microtubule-dependent process, during neuronal migration. Moreover, the PDK1–Akt pathway was found to control microtubules, likely by regulating the binding of accessory proteins including the dynactin subunit p150glued. Consistent with this notion, we found that PDK1 regulates the expression of cytoplasmic dynein intermediate chain and light intermediate chain at a posttranscriptional level in the developing neocortex. Our results thus reveal an essential role for the PDK1–Akt pathway in the regulation of a key step of neuronal migration.

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“…One common signaling pathway of EGF, FGF, and EPO is the phosphorylation of ERK1/2 through RAS and RAF kinases (Subramaniam and Unsicker, 2006). IGF1 signaling, on the other hand, leads to AKT phosphorylation by PI3K (Ye and D'Ercole, 2006), and AKT is involved in maintenance of neural precursor cells (Oishi et al, 2009). We hypothesized that LNK inhibits phosphorylation of ERK1/2 and AKT downstream of EGF, FGF, EPO, and IGF1 receptors.…”

Section: Lnk Suppresses Nspc Proliferation By Decreasing Growth Factomentioning

confidence: 99%

Adaptor Protein LNK Is a Negative Regulator of Brain Neural Stem Cell Proliferation after Stroke

et al. 2012

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Ischemic stroke causes transient increase of neural stem and progenitor cell (NSPC) proliferation in the subventricular zone (SVZ), and migration of newly formed neuroblasts toward the damaged area where they mature to striatal neurons. The molecular mechanisms regulating this plastic response, probably involved in structural reorganization and functional recovery, are poorly understood. The adaptor protein LNK suppresses hematopoietic stem cell self-renewal, but its presence and role in the brain are poorly understood. Here we demonstrate that LNK is expressed in NSPCs in the adult mouse and human SVZ. Lnk Ϫ/Ϫ mice exhibited increased NSPC proliferation after stroke, but not in intact brain or following status epilepticus. Deletion of Lnk caused increased NSPC proliferation while overexpression decreased mitotic activity of these cells in vitro. We found that Lnk expression after stroke increased in SVZ through the transcription factors STAT1/3. LNK attenuated insulin-like growth factor 1 signaling by inhibition of AKT phosphorylation, resulting in reduced NSPC proliferation. Our findings identify LNK as a stroke-specific, endogenous negative regulator of NSPC proliferation, and suggest that LNK signaling is a novel mechanism influencing plastic responses in postischemic brain.

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Selective induction of neocortical GABAergic neurons by the PDK1-Akt pathway through activation of Mash1

Abstract: GABAergic neuronal differentiation ͉ neural precursor cells ͉ telencephalon

Cited by 68 publications

References 48 publications

Forkhead box O transcription factors as possible mediators in the development of major depression

Forkhead box O transcription factors as possible mediators in the development of major depression

PDK1–Akt pathway regulates radial neuronal migration and microtubules in the developing mouse neocortex

Adaptor Protein LNK Is a Negative Regulator of Brain Neural Stem Cell Proliferation after Stroke

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