Abstract
Neural tube defects (NTDs), such as spina bifida (SB) or exencephaly, are common congenital malformations leading to infant mortality or severe disability. The etiology of NTDs is multifactorial with a strong genetic component. More than 70 NTD mouse models have been reported, suggesting the involvement of distinct pathogenetic mechanisms, including faulty cell death regulation. In this review, we focus on the contribution of functional genomics in elucidating the role of apoptosis and autophagy genes in neurodevelopment. On the basis of compared phenotypical analysis, here we discuss the relative importance of a tuned control of both apoptosome-mediated cell death and basal autophagy for regulating the correct morphogenesis and cell number in developing central nervous system (CNS). The pharmacological modulation of genes involved in these processes may thus represent a novel strategy for interfering with the occurrence of NTDs
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Abbreviations
- Ambra1:
-
activating molecule in Beclin 1-regulated autophagy
- ATG:
-
autophagy-related gene
- CNS:
-
central nervous system
- E:
-
embryonic day
- IP3:
-
myo-inositol-1,4,5-triphosphate
- Lamp:
-
lysosome-associated membrane protein
- NPC:
-
neuronal precursor cell
- NTDs:
-
neural tube defects
- PI3K:
-
phosphatidyl Inositol 3-kinase
- SB:
-
spina bifida
- TUNEL:
-
terminal uridine deoxynucleotidyl transferase dUTP nick end labeling
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Acknowledgements
This work was partially supported by grants from Fondazione Telethon, Compagnia di San Paolo, AIRC, The EU 7th Framework Programme, the Italian Ministry of University and Research (MUR) and the Italian Ministry of Health; FC is an Associate Telethon Scientist. We thank Martin W Bennet for the valuable editorial work and Marcello Giorgi for the drawings in Figure 1.
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Cecconi, F., Piacentini, M. & Fimia, G. The involvement of cell death and survival in neural tube defects: a distinct role for apoptosis and autophagy?. Cell Death Differ 15, 1170–1177 (2008). https://doi.org/10.1038/cdd.2008.64
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DOI: https://doi.org/10.1038/cdd.2008.64
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