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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)
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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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
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
Zeitschrift
Neuron
Quellenangaben
Band: 99,
Heft: 6,
Seiten: 1188-1203.e6
Verlag
Cell Press
Verlagsort
Cambridge, Mass.
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Developmental Genetics (IDG)