Entry, dispersion and differentiation of microglia in the developing central nervous system

Navascués, Julio; Calvente, Ruth; Marín‐Teva, José L.; Cuadros, Miguel A.

doi:10.1590/s0001-37652000000100013

Cited by 60 publications

(57 citation statements)

References 86 publications

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“…This supports the view that Mü ller cells are the substratum for radial migration of microglial cells in the avian retina, as previously suggested Navascués et al, 2000Navascués et al, , 2002. This is not surprising, because Mü ller cells are radially oriented retinal components.…”

Section: Radially Migrating Microglial Cells Adhere To Mü Ller Cell Rsupporting

confidence: 90%

“…Therefore, in situ studies of the central nervous system (CNS) are necessary to understand the cellular mechanisms of microglial migration. Studies of this type in the developing CNS revealed that microglial cells use tangential and radial migration to go from their entry points into the CNS to their final destinations (Navascués et al, 2000(Navascués et al, , 2002.…”

Section: Introductionmentioning

confidence: 99%

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

Sánchez‐López

Cuadros

Calvente

et al. 2004

Glia

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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.

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Section: Radially Migrating Microglial Cells Adhere To Mü Ller Cell Rsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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

Sánchez‐López

Cuadros

Calvente

et al. 2004

Glia

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“…The primitive microglial cells have a large cell body bral hemispheres from early neurogenesis and tend to increase in number during CNS differentiation. These observations corroborate the hypothesis presented by others (10) and are compatible with the descriptions of different areas of the CNS including the quail cerebellum (26), quail retina (22) and the prenatal rat hippocampus (27). Microglia constitute a significant part of the glial cell population, between 5 and 12% of the total number of CNS cells (28), and are distributed unevenly in the regions of the CNS (29,30).…”

Section: Discussionsupporting

confidence: 91%

“…In 16-day-old embryos the differentiation of neurons is sufficiently advanced to enable the distinction between neurons and glial cells by tritiated thymidine autoradiography (5,6). The neurons, astrocytes and oligodendrocytes arise from the neuroectoderm (7); however, the origin of microglial cells is still controversial (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

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Distribution of microglial cells in the cerebral hemispheres of embryonic and neonatal chicks

Ignácio

Müller

Carvalho

et al. 2005

Braz J Med Biol Res

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The distribution, morphology and morphometry of microglial cells in the chick cerebral hemispheres from embryonic day 4 (E4) to the first neonatal day (P1) were studied by histochemical labeling with a tomato (Lycopersicon esculentum) lectin. The histochemical analysis revealed lectin-reactive cells in the nervous parenchyma on day E4. Between E4 (5.7 ± 1.35 mm length) and E17 (8.25 ± 1.2 mm length), the lectin-reactive cells were identified as ameboid microglia and observed starting from the subventricular layer, distributed throughout the mantle layer and in the proximity of the blood vessels. After day E13, the lectin-reactive cells exhibited elongated forms with small branched processes, and were considered primitive ramified microglia. Later, between E18 (5.85 ± 1.5 mm cell body length) and P1 (3.25 ± 0.6 mm cell body length), cells with more elongated branched processes were observed, constituting the ramified microglia. Our findings provide additional information on the migration and differentiation of microglial cells, whose ramified form is observed at the end of embryonic development. The present paper focused on the arrangement of microglial cells in developing cerebral hemispheres of embryonic and neonatal chicks, which are little studied in the literature. Details of morphology, morphometry and spatial distribution of microglial cells contributed to the understanding of bird and mammal central nervous system ontogeny. Furthermore, the identification and localization of microglial cells during the normal development could be used as a morphological guide for embryonic brain injury researches.

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CX3CR1 mutation alters synaptic and astrocytic protein expression, topographic gradients, and response latencies in the auditory brainstem

Milinkeviciute

Chokr

Castro

et al. 2021

J of Comparative Neurology

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The precise and specialized circuitry in the auditory brainstem develops through adaptations of cellular and molecular signaling. We previously showed that elimination of microglia during development impairs synaptic pruning that leads to maturation of the calyx of Held, a large encapsulating synapse that terminates on neurons of the medial nucleus of the trapezoid body (MNTB). Microglia depletion also led to a decrease in glial fibrillary acidic protein (GFAP), a marker for mature astrocytes. Here, we investigated the role of signaling through the fractalkine receptor (CX3CR1), which is expressed by microglia and mediates communication with neurons. CX3CR1 −/− and wild-type mice were studied before and after hearing onset and at 9 weeks of age. Levels of GFAP were significantly increased in the MNTB in mutants at 9 weeks. Pruning was unaffected at the calyx of Held, but we found an increase in expression of glycinergic synaptic marker in mutant mice at P14, suggesting an effect on maturation of inhibitory inputs. We observed disrupted tonotopic gradients of neuron and calyx size in MNTB in mutant mice.Auditory brainstem recording (ABR) revealed that CX3CR1 −/− mice had normal thresholds and amplitudes but decreased latencies and interpeak latencies, particularly for the highest frequencies. These results demonstrate that disruption of fractalkine signaling has a significant effect on auditory brainstem development.Our findings highlight the importance of neuron-microglia-astrocyte communication in pruning of inhibitory synapses and establishment of tonotopic gradients early in postnatal development.

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Entry, dispersion and differentiation of microglia in the developing central nervous system

Cited by 60 publications

References 86 publications

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

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

Distribution of microglial cells in the cerebral hemispheres of embryonic and neonatal chicks

CX3CR1 mutation alters synaptic and astrocytic protein expression, topographic gradients, and response latencies in the auditory brainstem

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