Endocytosis and autophagy in dying neurons: an ultrastructural study in chick embryos.
In an effort to understand naturally occurring neuronal death in the developing isthmo-optic nucleus, we have accentuated one of its most probably causes, failure to receive adequate trophic maintenance from the axonal terminal zone in the retina, and have studied the dying neurons ultrastructurally. Retrograde trophic maintenance was blocked by means of intraocularly injected colchicine, which caused all the isthmo-optic neurons to die by just one of the two or more kinds of cell death that they undergo during normal development. The present paper deals with the very prominent cytoplasmic aspects of this kind of cell death, notably the uptake of exogeneous horseradish peroxidase and autophagy. There were also nuclear changes, which are dealt with mainly in the accompanying paper (Clarke and Hornung, J. Comp. Neurol. 283:438-449,'89). Numerous cytoplasmic vacuoles occurred in both soma and dendrites, and they were of three main kinds, of which the smallest (less than 0.5 microns diameter) had unstructured contents, whereas the larger two (1-2 microns and 2-7 microns) were secondary lysosomes (mostly residual bodies). Intravascularly injected horseradish peroxidase labeled all three kinds of vacuole but not the free cytoplasm, indicating that the uptake was by endocytosis rather than by leakage through holes in the membrane, as is confirmed by our failure to detect any such holes. We suspect that the smallest vacuoles are the primary endosomes, that these subsequently fuse with vacuoles of the intermediate kind, and that the largest vacuoles are formed by the fusion of these latter. The purpose of the endocytosis may be to channel the plasma membrane piecemeal into the lysosomes for destruction.
Hornung
J P
JP
Institute of Anatomy, University of Lausanne, Switzerland.
Koppel
H
H
Clarke
P G
PG
D000818:Animals; D001343:Autophagy; D002454:Cell Differentiation; D002470:Cell Survival; D002642:Chick Embryo; D003593:Cytoplasm / Q000648:ultrastructure; D003712:Dendrites / Q000648:ultrastructure; D004705:Endocytosis; D008854:Microscopy, Electron; D009410:Nerve Degeneration; D009474:Neurons / Q000166:cytology; D010587:Phagocytosis; D012160:Retina / Q000166:cytology*; D013477:Superior Colliculi / Q000166:cytology*; D014617:Vacuoles / Q000648:ultrastructure; D014795:Visual Pathways / Q000166:cytology