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FoxO function is essential for maintenance of autophagic flux and neuronal morphogenesis in adult neurogenesis.
Neuron 99, 1188-1203.e6 (2018)
Publ. Version/Full Text
DOI
PMC
Autophagy is a conserved catabolic pathway with emerging functions in mammalian neurodevelopment and human neurodevelopmental diseases. The mechanisms controlling autophagy in neuronal development are not fully understood. Here, we found that conditional deletion of the Forkhead Box O transcription factors FoxO1, FoxO3, and FoxO4 strongly impaired autophagic flux in developing neurons of the adult mouse hippocampus. Moreover, FoxO deficiency led to altered dendritic morphology, increased spine density, and aberrant spine positioning in adult-generated neurons. Strikingly, pharmacological induction of autophagy was sufficient to correct abnormal dendrite and spine development of FoxO-deficient neurons. Collectively, these findings reveal a novel link between FoxO transcription factors, autophagic flux, and maturation of developing neurons.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Foxo ; Adult Neurogenesis ; Aging ; Autism ; Autophagy ; Hippocampus ; Spines ; Stem Cells; Neural Stem-cells; Autism Spectrum Disorders; Dentate Granule Cells; In-vivo; Transcription Factors; Mammalian Autophagy; Alzheimers-disease; Homeostasis; Clearance; Degradation
ISSN (print) / ISBN
0896-6273
e-ISSN
1097-4199
Journal
Neuron
Quellenangaben
Volume: 99,
Issue: 6,
Pages: 1188-1203.e6
Publisher
Cell Press
Publishing Place
Cambridge, Mass.
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Developmental Genetics (IDG)