FoxO Function Is Essential for Maintenance of Autophagic Flux and Neuronal Morphogenesis in Adult Neurogenesis

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2018 Sep 11

PMID 30197237

Citations 66

Authors

Iris Schaffner

Georgia Minakaki

M Amir Khan

Elli-Anna Balta

Ursula Schlotzer-Schrehardt

Tobias J Schwarz

Ruth Beckervordersandforth

Beate Winner

Ashley E Webb

Ronald A DePinho

Jihye Paik

Wolfgang Wurst

Jochen Klucken

D Chichung Lie

Affiliations

Soon will be listed here.

Abstract

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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