@article{c9a0c1f419074997bc9f7ffb4cefed11,
title = "FoxO Function Is Essential for Maintenance of Autophagic Flux and Neuronal Morphogenesis in Adult Neurogenesis",
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. Sch{\"a}ffner et al. identify FoxO transcription factors as critical regulators of autophagic flux in adult hippocampal neurogenesis and show that FoxO-dependent autophagic flux is necessary for morphological maturation and synaptic integration of adult-born hippocampal neurons.",
keywords = "FoxO, adult neurogenesis, aging, autism, autophagy, hippocampus, spines, stem cells",
author = "Iris Sch{\"a}ffner and Georgia Minakaki and Khan, {M. Amir} and Balta, {Elli Anna} and Ursula Schl{\"o}tzer-Schrehardt and Schwarz, {Tobias J.} and Ruth Beckervordersandforth and Beate Winner and Webb, {Ashley E.} and DePinho, {Ronald A.} and Jihye Paik and Wolfgang Wurst and Jochen Klucken and Lie, {D. Chichung}",
note = "Funding Information: We thank M. G{\"o}tz (LMU Munich) for providing the GLAST::CreER T2 mice. We thank S. Jessberger for helpful discussions and comments on the manuscript. This work was supported by grants from the German Research Foundation (DFG, LI 858/6-3 and 9-1 to D.C.L.; INST 410/45-1 FUGG ; BE 5136/1-2 and 2-1 to R.B.; KL 1395/8-1 to J.K.; and WU 164/5-1 and CRC870 to W.W.); the Bavarian Research Network “ForIPS” to D.C.L., J.K., B.W., and W.W.; the University Hospital Erlangen (IZKF grants E12 and E16 to D.C.L., E21 to D.C.L. and J.K., and E25 to B.W.); the German Federal Ministry of Education and Research ( BMBF 01GQ113 , 01GM1520A , and 01EK1609B to B.W., and Integrament 01ZX1314H to W.W.); and the NIH ( AG048284 to J.P. and AG053268 to A.E.W.). R.B. is an associated fellow of the research training group 2162 “Neurodevelopment and Vulnerability of the Central Nervous System” of the Deutsche Forschungsgemeinschaft (DFG GRK2162/1). Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2018",
month = sep,
day = "19",
doi = "10.1016/j.neuron.2018.08.017",
language = "English (US)",
volume = "99",
pages = "1188--1203.e6",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "6",
}