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

Schäffner I, Minakaki G, Khan MA, Balta EA, Schlötzer-Schrehardt U, Schwarz TJ, Beckervordersandforth R, Winner B, Webb AE, Depinho RA, Paik J, Wurst W, Klucken J, Lie DC (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Neuron Elsevier (Cell Press)

Book Volume: 99

Pages Range: 1188-1203.e6

Journal Issue: 6

DOI: 10.1016/j.neuron.2018.08.017

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.

Authors with CRIS profile

Iris Schäffner Institut für Biochemie Georgia Minakaki Professur für Molekulare Neurologie Elli-Anna Balta Lehrstuhl für Biochemie und Pathobiochemie Ursula Schlötzer-Schrehardt Medizinische Fakultät Ruth Beckervordersandforth-Bonk Lehrstuhl für Biochemie und Pathobiochemie Beate Winner Professur für Stammzell-Modelle seltener neuraler Erkrankungen Jochen Klucken Department of Molecular Neurology Dieter Chichung Lie Institut für Biochemie

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Involved external institutions

Technische Universität München (TUM) DE Germany (DE) Brown University US United States (USA) (US) University of Texas MD Anderson Cancer Center US United States (USA) (US) Cornell University US United States (USA) (US)

How to cite

APA:

Schäffner, I., Minakaki, G., Khan, M.A., Balta, E.-A., Schlötzer-Schrehardt, U., Schwarz, T.J.,... Lie, D.C. (2018). FoxO Function Is Essential for Maintenance of Autophagic Flux and Neuronal Morphogenesis in Adult Neurogenesis. Neuron, 99(6), 1188-1203.e6. https://dx.doi.org/10.1016/j.neuron.2018.08.017

MLA:

Schäffner, Iris, et al. "FoxO Function Is Essential for Maintenance of Autophagic Flux and Neuronal Morphogenesis in Adult Neurogenesis." Neuron 99.6 (2018): 1188-1203.e6.

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