FoxO Function Is Essential for Maintenance of Autophagic Flux and Neuronal Morphogenesis in Adult Neurogenesis. Academic Article uri icon

Overview

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.

publication date

  • September 6, 2018

Research

keywords

  • Autophagy
  • Forkhead Transcription Factors
  • Morphogenesis
  • Neurogenesis

Identity

PubMed Central ID

  • PMC6186958

Scopus Document Identifier

  • 85053338479

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2018.08.017

PubMed ID

  • 30197237

Additional Document Info

volume

  • 99

issue

  • 6