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

Abstract

Microglial cells spread within the nervous system by tangential and radial migration. The cellular mechanism of tangential migration of microglia has been described in the quail retina but the mechanism of their radial migration has not been studied. In this work, we clarify some aspects of this mechanism by analyzing morphological features of microglial cells at different steps of their radial migration in the quail retina. Microglial cells migrate in the vitreal half of the retina by successive jumps from the vitreal border to progressively more scleral levels located at the vitreal border, intermediate regions, and scleral border of the inner plexiform layer (IPL). The cellular mechanism used for each jump consists of the emission of a leading thin radial process that ramifies at a more scleral level before retraction of the rear of the cell. Hence, radial migration and ramification of microglial cells are simultaneous events. Once at the scleral border of the IPL, microglial cells migrate through the inner nuclear layer to the outer plexiform layer by another mechanism: they retract cell processes, become round, and squeeze through neuronal bodies. Microglial cells use radial processes of s-lamininexpressing Mü ller cells as substratum for radial migration. Levels where microglial cells stop and ramify at each jump are always interfaces between retinal strata with strong tenascin immunostaining and strata showing weak or no tenascin immunoreactivity. When microglial cell radial migration ends, tenascin immunostaining is no longer present in the retina. These findings suggest that tenascin plays a role in the stopping and ramification of radially migrating microglial cells.

Embryonic and postnatal development of microglial cells in the mouse retina

“…This distribution pattern is similar to previous reports on various species (Schnitzer, 1989;Navascués et al, 1994;Harada et al, 2002;Hughes et al, 2003). Although the presence of microglial cells in the OPL of some species has been debated (see Schnitzer, 1989), our results clearly demonstrate their presence in the OPL of the mouse retina, as reported in birds (Navascués et al, 1994;Sá nchez-López et al, 2004) and rabbits (Schnitzer, 1989). We highlight the presence of some microglial cell bodies in the INL of the adult mouse retina, contrasting with descriptions in quail retina, in which microglial cells are seen in the INL during development but not at adulthood (Navascués et al, 1994;Marín-Teva et al, 1999c).…”

“…Thus, microglial cells in the developing quail retina migrate by adhering to Mü ller cell processes (Marín-Teva et al, 1998;Sá nchezLópez et al, 2004), and the extracellular molecule tenascin appears to regulate microglial cell ramification (Sá nchez-López et al, 2004). However, similar mechanisms have yet to be elucidated in the mouse retina.…”

Behavior of in vitro cultured ameboid microglial cells migrating on Müller cell end‐feet in the quail embryo retina

“…The C4 mAb labels M€ uller cell radial processes but not MCEF (Sanchez-Lopez et al, 2004). At 0 hiv, vitreal ends of these processes were seen in ILM/MECF sheets as C4-positive dots with diameter of 1-2 lm (Fig.…”

“…MCEF were labeled with JG22 mAb, which was raised against the b1 subunit of avian integrins (Hofer et al, 1990;Hynes, 2004); in the retina, this mAb specifically labels the surface of developing and mature M€ uller cells and is highly concentrated at their end-feet (Hering et al, 2000). C4 mAb recognizes s-laminin, which is expressed in the retina by M€ uller cells (Libby et al, 1997;Sanchez-Lopez et al, 2004); it was used to label broken ends of M€ uller cell radial processes connecting with MCEF.…”

“…Previous studies by our group (Marın-Teva et al, 1998;Navascues et al, 1995;Sanchez-Lopez et al, 2004) showed that ameboid microglial cells enter the retina of quail embryos at the site of the insertion of the pecten into the optic nerve head. Then, they migrate tangentially in a central-to-peripheral direction on the vitreal part of the embryonic retina.…”