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Journal Article

The autophagy regulators Ambra1 and Beclin 1 are required for adult neurogenesis in the brain subventricular zone.

MPS-Authors
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Tonchev,  A. B.
Research Group of Molecular Developmental Neurobiology, MPI for biophysical chemistry, Max Planck Society;

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Stoykova,  A.
Research Group of Molecular Developmental Neurobiology, MPI for biophysical chemistry, Max Planck Society;

Fulltext (public)

2057008.pdf
(Publisher version), 3MB

2057008_Suppl_4.pdf
(Publisher version), 187KB

Supplementary Material (public)

2057008_Suppl_1.pdf
(Supplementary material), 87KB

2057008_Suppl_2.pdf
(Supplementary material), 128KB

2057008_Suppl_3.pdf
(Supplementary material), 121KB

2057008_Suppl_5.pdf
(Supplementary material), 175KB

2057008_Suppl_6.pdf
(Supplementary material), 147KB

2057008_Suppl_7.pdf
(Supplementary material), 64KB

Citation

Yazdankhah, M., Farioli-Vecchioli, S., Tonchev, A. B., Stoykova, A., & Cecconi, F. (2014). The autophagy regulators Ambra1 and Beclin 1 are required for adult neurogenesis in the brain subventricular zone. Cell Death and Disease, 5: e1403. doi:10.1038/cddis.2014.358.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0023-D0CD-F
Abstract
Autophagy is a conserved proteolytic mechanism required for maintaining cellular homeostasis. The role of this process in vertebrate neural development is related to metabolic needs and stress responses, even though the importance of its progression has been observed in a number of circumstances, both in embryonic and in postnatal differentiating tissues. Here we show that the proautophagic proteins Ambra1 and Beclin 1, involved in the initial steps of autophagosome formation, are highly expressed in the adult subventricular zone (SVZ), whereas their downregulation in adult neural stem cells in vitro leads to a decrease in cell proliferation, an increase in basal apoptosis and an augmented sensitivity to DNA-damage-induced death. Further, Beclin 1 heterozygosis in vivo results in a significant reduction of proliferating cells and immature neurons in the SVZ, accompanied by a marked increase in apoptotic cell death. In sum, we propose that Ambra1- and Beclin 1-mediated autophagy plays a crucial role in adult neurogenesis, by controlling the survival of neural precursor cells.