Autophagy and its cross-talk with cell death in neural development

The study of autophagy-deficient model systems has made it possible to appreciate the importance of a correctly functioning autophagic machinery in the development of both lower and higher eukaryotes. Autophagy is crucial to embryogenesis, potentially acting in parallel with apoptosis to remodel tissues. An increase in autophagic cells is observed during embryonic stages characterized by massive cell elimination, such as the complex events of fly and worm metamorphosis. Moreover, autophagy probably protects cells during metabolic stress and nutrient paucity, which both occur during the tissue remodeling of embryogenesis. Several lines of evidence also highlight the importance of autophagy in later stages of embryonic and postnatal development. Thus, it can be concluded that there is a close interplay between autophagy and the processes of cell death, proliferation and differentiation, and that correct central nervous system (CNS) development depends upon an intact autophagic machinery.