Tangential migration of ameboid microglia in the developing quail retina: Mechanism of migration and migratory behavior

Abstract

Long distance migration of microglial precursors within the central nervous system is essential for microglial colonization of the nervous parenchyma. We studied morphological features of ameboid microglial cells migrating tangentially in the developing quail retina to shed light on the mechanism of migration and migratory behavior of microglial precursors. Many microglial precursors remained attached on retinal sheets containing the inner limiting membrane covered by a carpet of Mu ¨ller cell endfeet. This demonstrates that most ameboid microglial cells migrate tangentially on Mu ¨ller cell endfeet. Many of these cells showed a central-to-peripheral polarized morphology, with extensive lamellipodia spreading through grooves flanked by Mu ¨ller cell radial processes, to which they were frequently anchored. Low protuberances from the vitreal face of microglial precursors were firmly attached to the subjacent basal lamina, which was accessible through gaps in the carpet of Mu ¨ller cell endfeet. These results suggest a mechanism of migration involving polarized extension of lamellipodia at the leading edge of the cell, strong cell-to-substrate attachment, translocation of the cell body forward, and retraction of the rear of the cell. Other ameboid cells were multipolar, with lamellipodial projections radiating in all directions from the cell body, suggesting that microglial precursors explore the surrounding environment to orient their movement. Central-to-peripheral migration of microglial precursors in the retina does not follow a straight path; instead, these cells perform forward, backward, and sideways movements, as suggested by the occurrence of (a) V-shaped bipolar ameboid cells with their vertex pointing toward either the center or the periphery of the retina, and (b) threadlike processes projecting from either the periphery-facing edge or the center-facing edge of ameboid microglial cells.

Radial migration of developing microglial cells in quail retina: A confocal microscopy study

“…Amoeboid microglial cells migrated tangentially on endfeet of Mü ller cells in the vitreal part of the quail embryonic retina (Marín-Teva et al, 1998). In the present study, this vitreal part was termed level 0 (L0), in which migrating microglial cells were amoeboid in shape and did not ramify.…”

“…The adult quail retina contains a dense network of ramified microglia (Navascués et al, 1994), which derive from amoeboid microglial cells that enter the developing retina between 7 and 16 days of incubation (E7-E16). They enter from the optic nerve head and the base of the pecten and then migrate tangentially on its vitreal surface in contact with Mü ller cell endfeet in a central-to-peripheral direction (Navascués et al, 1995;Marín-Teva et al, 1998). From E9 to the first half of the first posthatching week, microglial cells migrating on the vitreal surface of the retina can move radially in a vitreal-to-scleral direction to gain access to the inner plexiform layer (IPL) and the outer plexiform layer (OPL), where they become ramified microglia (Navascués et al, 1995;Marín-Teva et al, 1999c).…”

“…Some aspects of the mechanism of tangential migration of microglia in the quail retina have been clarified (Marín-Teva et al, 1998). Tangentially migrating amoeboid microglial cells are elongated in shape and emit broad lamellipodia that adhere to Mü ller cell endfeet.…”

The origin and differentiation of microglial cells during development

“…Brain macrophages and immature microglia in the developing CNS also have mitotic activity, as revealed by the uptake of labeled nucleotides or by the presence of proliferating cell nuclear antigen (PCNA) (Mander and Morris, 1996;Cossmann et al, 1997;Dalmau, 1997;MarõÂ n-Teva et al, 1998). The relative contribution of proliferation to the increase in number of microglial cells during development has not been established.…”

“…In the ®rst stage, ameboid microglia, have morphological, histochemical and immunological features similar to those of macrophages outside the CNS, and are therefore also known as brain macrophages. Ameboid microglia are round or have short, broad processes; presumably, cells of dendritic or elongated morphology also belong to this type of microglia, as seen in the developing retina, tectum and cerebellum of the quail Navascue s et al, 1995;Marõ n-Teva et al, 1998). Part of the ameboid cells present in the embryonic brain may degenerate (Dalmau, 1997), as occurs with activated microglia in the adult brain (Reid et al, 1993;Gehrmann and Banati, 1995;Jones et al, 1997), but many of them would develop thin processes and become rami®ed.…”