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Article Addendum
A Novel Role for Autophagy in Neurodevelopment
Francesco Cecconi, Sabrina Di Bartolomeo, Roberta Nardacci, Claudia Fuoco, Marco Corazzari, Luigi Giunta, Alessandra Romagnoli, Anastassia Stoykova, Kamal Chowdhury, Gian Maria Fimia and Mauro Piacentini
volume 3 | issue 5
September/October 2007Pages: 505 - 507
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We recently showed that Ambra1, a WD40-containing ~130 KDa protein, is a novel activating molecule in Beclin 1-regulated autophagy and plays a role in the development of the nervous system. Ambra1 binds to Beclin 1 and favors Beclin 1/Vps34 interaction. At variance with these factors, Ambra1 is highly conserved among vertebrates only, and its expression is mostly confined to the neuroepithelium during early neurogenesis. Ambra1 functional inactivation in mouse led to lethality in utero (starting from embryonic day 14.5), characterized by severe neural tube defects associated with autophagy impairment, unbalanced cell proliferation, accumulation of ubiquitinated proteins, and excessive apoptosis. We also demonstrated that hyperproliferation was the earliest detectable abnormality in the developing neuroepithelium, followed by a wave of caspase-dependent cell death. These findings provided in vivo evidence supporting the existence of a complex interplay between autophagy, cell proliferation and cell death during neural development in mammals. In this Addendum, we review our findings in the contexts of autophagy and neurodevelopment and consider some of the issues raised.
Addendum to:
Ambra1 Regulates Autophagy and the Development of the Nervous System
G.M. Fimia, A. Stoykova, A. Romagnoli, L. Giunta, S. Di Bartolomeo, R. Nardacci, M. Corazzari, C. Fuoco, A. Ucar, P. Schwartz, P. Gruss, M. Piacentini, K. Chowdhury and F. Cecconi
Nature 2007; In press
Authors
Francesco Cecconi
Dulbecco Telethon Institute
Sabrina Di Bartolomeo
University of Rome Tor Vergata
Roberta Nardacci
National Institute for Infectious Diseases IRCCS 'L. Spallanzani'
Claudia Fuoco
University of Tor Vergata
Marco Corazzari
National Institute for Infectious Diseases IRCCS 'L. Spallanzani'
Luigi Giunta
University of Rome Tor Vergata
Alessandra Romagnoli
National Institute for Infectious Diseases IRCCS 'L. Spallanzani'
Anastassia Stoykova
Max-Planck-Institute of Biophysical Chemistry
Kamal Chowdhury
Max-Planck-Institute of Biophysical Chemistry
Gian Maria Fimia
National Institute for Infectious Diseases IRCCS 'L. Spallanzani'
Mauro Piacentini
University of Rome Tor Vergata
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.