Macrophages during avian optic nerve development: relationship to cell death and differentiation into microglia

Cell death is frequent during the development of the nervous system. In the developing optic nerve of chicks and quails, neuroepithelial cell death was first observable on the third day of incubation, slightly after the first cell ganglion axons appeared in the stalk. Specialized phagocytes were observed within the stalk in chronological and topographical coincidence with cell death. These cells were identified as macrophages because of their morphological features, intense acid phosphatase activity and, in quail embryos, labeling with QH1, a monoclonal antibody recognizing quail hemangioblastic cells. Macrophages in areas of cell death were round and actively phagocytosed cell debris. We used electron microscopy and histochemical and immunocytochemical labeling to study macrophagic cells of the optic nerve in avian embryos of 3-6.5 days of incubation. As development proceeded, phagocytosing, round macrophages became ameboid macrophages that migrated from areas of cell death toward regions occupied by optic axonal fascicles. Macrophages in these locations were thin and elongated, with a few processes. To elucidate the final fate of macrophagic cells in the optic nerve, sections taken from older embryonic and hatched quails were stained with the QH1 antibody. On the 8th day of incubation some slightly ramified QH1+ cells were present among axonal fascicles. In subsequent stages these cells increased in number and acquired more complex ramifications. In adult optic nerves, QH1+ cells had a small body and sent out slender processes, sometimes with secondary and tertiary branches, which were frequently orientated parallel to the course of the optic axons. These cells were considered to be microglial cells. The appearance of macrophages within the developing optic nerve at the same time as neuroepithelial cell death suggests that cell death influences the recruitment of macrophages into the nerve. When macrophages reach the areas invaded by optic axonal fascicles, they undergo structural and probably also physiological changes that appear to signal differentiation into microglia.