We recently showed that Ambra 1, a WD40-containing similar to 130 KDa protein, is a novel activating molecule in Beclin 1-regulated autophagy and plays a role in the development of the nervous system. Ambra 1 binds to Beclin 1 and favors Beclin 1/Vps34 interaction. At variance with these factors, Ambra I 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 article, we review our findings in the contexts of autophagy and neurodevelopment and consider some of the issues raised.

Cecconi, F., DI BARTOLOMEO, S., Nardacci, R., Fuoco, C., Corazzari, M., Giunta, L., et al. (2007). A novel role for autophagy in neurodevelopment. AUTOPHAGY, 3(5), 506-508.

A novel role for autophagy in neurodevelopment

CECCONI, FRANCESCO;DI BARTOLOMEO, SABRINA;Fuoco, C;CORAZZARI, MARCO;PIACENTINI, MAURO
2007-01-01

Abstract

We recently showed that Ambra 1, a WD40-containing similar to 130 KDa protein, is a novel activating molecule in Beclin 1-regulated autophagy and plays a role in the development of the nervous system. Ambra 1 binds to Beclin 1 and favors Beclin 1/Vps34 interaction. At variance with these factors, Ambra I 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 article, we review our findings in the contexts of autophagy and neurodevelopment and consider some of the issues raised.
2007
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/06 - ANATOMIA COMPARATA E CITOLOGIA
English
Con Impact Factor ISI
Apoptosis; Beclin 1; Differentiation; Embryogenesis; Neural folds; Neuroepithelium; Sonic hedgehog
http://www.landesbioscience.com/journals/autophagy/article/4616
Cecconi, F., DI BARTOLOMEO, S., Nardacci, R., Fuoco, C., Corazzari, M., Giunta, L., et al. (2007). A novel role for autophagy in neurodevelopment. AUTOPHAGY, 3(5), 506-508.
Cecconi, F; DI BARTOLOMEO, S; Nardacci, R; Fuoco, C; Corazzari, M; Giunta, L; Romagnoli, A; Stoykova, A; Chowdhury, K; Fimia, G; Piacentini, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/35146
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