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Articles, Cellular/Molecular

FoxG1 Promotes the Survival of Postmitotic Neurons

Somasish Ghosh Dastidar, Paul Michael Zagala Landrieu and Santosh R. D'Mello
Journal of Neuroscience 12 January 2011, 31 (2) 402-413; DOI: https://doi.org/10.1523/JNEUROSCI.2897-10.2011
Somasish Ghosh Dastidar
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Paul Michael Zagala Landrieu
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Santosh R. D'Mello
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Abstract

The transcription factor FoxG1 regulates neurogenesis in the embryonic telencephalon as well as a number of other neurodevelopmental processes. While FoxG1 continues to be expressed in neurons postnatally and through adulthood, its role in fully differentiated neurons is not known. The current study demonstrates that FoxG1 promotes the survival of postmitotic neurons. In cerebellar granule neurons primed to undergo apoptosis, FoxG1 expression is reduced. Ectopic expression of FoxG1 blocks neuronal death, whereas suppression of its expression induces death in otherwise healthy neurons. The first 36 residues of FoxG1 are necessary for its survival-promoting effect, while the C-terminal half of the protein is dispensable. Mutation of Asp219, a residue necessary for DNA binding, abrogates survival promotion by FoxG1. Survival promotion is also eliminated by mutation of Thr271, a residue phosphorylated by Akt. Pharmacological inhibition of Akt blocks the survival effects of wild-type FoxG1 but not forms in which Thr271 is replaced with phosphomimetic residues. Treatment of neurons with IGF-1, a neurotrophic factor that promotes neuronal survival by activating Akt, prevents the apoptosis-associated downregulation of FoxG1 expression. Moreover, the overexpression of dominant-negative forms of FoxG1 blocks the ability of IGF-1 to maintain neuronal survival suggesting that FoxG1 is a downstream mediator of IGF-1/Akt signaling. Our study identifies a new and important function for FoxG1 in differentiated neurons.

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The Journal of Neuroscience: 31 (2)
Journal of Neuroscience
Vol. 31, Issue 2
12 Jan 2011
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FoxG1 Promotes the Survival of Postmitotic Neurons
Somasish Ghosh Dastidar, Paul Michael Zagala Landrieu, Santosh R. D'Mello
Journal of Neuroscience 12 January 2011, 31 (2) 402-413; DOI: 10.1523/JNEUROSCI.2897-10.2011

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FoxG1 Promotes the Survival of Postmitotic Neurons
Somasish Ghosh Dastidar, Paul Michael Zagala Landrieu, Santosh R. D'Mello
Journal of Neuroscience 12 January 2011, 31 (2) 402-413; DOI: 10.1523/JNEUROSCI.2897-10.2011
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