Parnaik, Rahul; (1997) Cell death and clearance in young animals. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

This thesis explores the recognition, engulfment, and degradation of cells dying by programmed cell death (PCD), by phagocytes. PCD is an important process in animal development where cells actively participate in their own demise. The thesis begins with a light and electron microscope survey of the phagocytes in the neonatal rodent optic nerve and cerebellum and shows that different combinations of cells phagocytose the dead cells in different locations; microglia in the optic nerve, Bergmann glia and neuroblasts in the cerebellar external granular layer (EGL), and microglia and astrocytes in the cerebellar white matter. The events of recognition, engulfment, and degradation are then examined in detail using a time-lapse system to observe different phagocytic cell types engulfmg pyknotic cells. Microglia, the professional phagocytes of the central nervous system (CNS), engulf pyknotic cells on first contact, whereas other, nonprofessional phagocytes (BHKs, lens epithelial cells, and astrocytes), recognise dead cells and throw membrane ruffles around them, but only ingest them after a period of time has elapsed. Moreover, microglia digest pyknoses more rapidly than non-professionals. These results were corroborated with in vivo electron microscope data showing that pyknoses in the optic nerve are always completely engulfed by microglia and are digested more rapidly than pyknoses in the cerebellar EGL, which are palpated by neighbouring neuroblasts before their ingestion, and subsequently digested more slowly. Irradiation of the neonatal cerebellum selectively causes PCD of large numbers of neuroblasts. Most of the pyknoses are engulfed by Bergmann glia, revealing the unexpectedly large phagocytic capacity of these cells. Moreover, the irradiation causes microglia, which are normally absent from the EGL, to be transiently recruited into it, suggesting a chemotactical response to dying cells.

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