Apoptosome impairment during development results in activation of an autophagy program in cerebral cortex.
The deficiency of upstream regulators of the mitochondrial death pathway has been recently shown to trigger in vitro a cellular process of self-clearance with features of autophagy. We show here that, when Apaf1 (responsible for apoptosome formation) is downregulated in vivo in cortical precursors, cells express markers of neuronal differentiation, accumulate in ectopic cortical masses and show hallmarks of the beclin-1-dependent pathway of autophagy, probably activated by a depletion in growth factors in the cells' microenvironment. To visualize this process in a cell culture model system, we also used a neural precursor cell line to mimic growth factor starvation in the absence of the apoptosome and tracked autophagolysosome formation. Our findings demonstrate the existence of an interplay between the autophagy and apoptosis pathways in vivo in brain development, and possibly link the absence of apoptosis to the occurrence of pathological conditions associated with peculiar cellular morphotypes.
Moreno
Sandra
S
Department of Biology-LIME, University Roma Tre, 00146, Rome, Italy.
Imbroglini
Valentina
V
Ferraro
Elisabetta
E
Bernardi
Cinzia
C
Romagnoli
Alessandra
A
Berrebi
Albert S
AS
Cecconi
Francesco
F
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics / Q000502:physiology; D001343:Autophagy / Q000502:physiology*; D002540:Cerebral Cortex / Q000196:embryology*; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000473:pathology; D013217:Starvation / Q000473:pathology
C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1