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Basic Research Paper

Autophagy is not universally required for phosphatidyl-serine exposure and apoptotic cell engulfment during neural development

María A. Mellén, Enrique J. de la Rosa and Patricia Boya

Apoptosis and autophagy are physiological processes implicated in the maintenance of cell and tissue homeostasis. We took advantage of the existence of multiple phases of
developmental cell death in the embryonic chick retina and of the availability of shortterm organotypic retinal cultures to approach the possible relationship between
apoptosis and autophagy during neural development. We examined retinas at embryonic day 5, an early stage at which cell death is related to eye morphogenesis and to retinal
ganglion cell generation, as well as at embryonic day 9, when cell death is associated with neurotrophic support of the retinal ganglion cells. Exposure to 3-methyl-adenine, a
classical inhibitor of autophagy, elicited a selective accumulation of apoptotic bodies in the dorsotemporal area of embryonic day 5 retinas where neurogenesis is taking place.
This accumulation was correlated with a blockage of phosphatidyl-serine presentation and, consequently, with a lack of engulfment of the dying cells by their neighbors. In
striking contrast, none of these phenomena were observed in association with cell death in the optic nerve and optic fissure at embryonic day 5, or in embryonic day 9 retinas.
Our data suggest that autophagy is essential for phosphatidyl-serine presentation by apoptotic cells during the phase of cell death associated to neurogenesis, but this is not a
universal requirement for all phases of cell death occurring during retinal development.

Authors

María A. Mellén

3D Lab (Development, Differentiation & Degeneration); Cellular and Molecular Medicine; Centro de Investigaciones Biológicas; CSIC; Madrid, Spain

Enrique J. de la Rosa Corresponding author: ejdelarosa@cib.csic.es

3D Lab (Development, Differentiation & Degeneration); Cellular and Molecular Medicine; Centro de Investigaciones Biológicas; CSIC; Madrid, Spain

Patricia Boya Corresponding author: pboya@cib.csic.es

3D Lab (Development, Differentiation & Degeneration); Cellular and Molecular Medicine; Centro de Investigaciones Biológicas; CSIC; Madrid, Spain