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

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

Neuron (2018-09-11)
Iris Schäffner, Georgia Minakaki, M Amir Khan, Elli-Anna Balta, Ursula Schlötzer-Schrehardt, Tobias J Schwarz, Ruth Beckervordersandforth, Beate Winner, Ashley E Webb, Ronald A DePinho, Jihye Paik, Wolfgang Wurst, Jochen Klucken, D Chichung Lie
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.

MATERIALS
Product Number
Brand
Product Description

Millipore
Accutase cell detachment solution, A cell detachment solution of proteolytic & collagenolytic enzymes. The reagent is useful for creating single cell suspensions from clumped cell cultures for accurate cell counting, detachment of cells from primary tissue.
Sigma-Aldrich
Nunc® MicroWell® MiniTrays, 60 well MicroWell MiniTray for serological applications, non-treated, polystyrene, non-sterile, 100/cs
Sigma-Aldrich
Ribonuclease A from bovine pancreas, Type II-A, ≥60% (SDS-PAGE), >= 60 Kunitz units/mg protein