Limits...
Neuronal and microglial regulators of cortical wiring: usual and novel guideposts.

Squarzoni P, Thion MS, Garel S - Front Neurosci (2015)

Bottom Line: In the last decades, tangential migrating neurons have also been found to participate in the guidance of principal axonal tracts in the forebrain.We furthermore found that microglia participate to the shaping of prenatal forebrain circuits, thereby opening novel perspectives on forebrain development and wiring.Here we will review the last findings on already known guidepost cell populations and will discuss the role of microglia as a potentially new class of atypical guidepost cells.

View Article: PubMed Central - PubMed

Affiliation: Centre National de la Recherche Scientifique UMR8197, Ecole Normale Supérieure, Institut de Biologie, Institut National de la Santé et de la Recherche Médicale U1024 Paris, France.

ABSTRACT
Neocortex functioning relies on the formation of complex networks that begin to be assembled during embryogenesis by highly stereotyped processes of cell migration and axonal navigation. The guidance of cells and axons is driven by extracellular cues, released along by final targets or intermediate targets located along specific pathways. In particular, guidepost cells, originally described in the grasshopper, are considered discrete, specialized cell populations located at crucial decision points along axonal trajectories that regulate tract formation. These cells are usually early-born, transient and act at short-range or via cell-cell contact. The vast majority of guidepost cells initially identified were glial cells, which play a role in the formation of important axonal tracts in the forebrain, such as the corpus callosum, anterior, and post-optic commissures as well as optic chiasm. In the last decades, tangential migrating neurons have also been found to participate in the guidance of principal axonal tracts in the forebrain. This is the case for several examples such as guideposts for the lateral olfactory tract (LOT), corridor cells, which open an internal path for thalamo-cortical axons and Cajal-Retzius cells that have been involved in the formation of the entorhino-hippocampal connections. More recently, microglia, the resident macrophages of the brain, were specifically observed at the crossroads of important neuronal migratory routes and axonal tract pathways during forebrain development. We furthermore found that microglia participate to the shaping of prenatal forebrain circuits, thereby opening novel perspectives on forebrain development and wiring. Here we will review the last findings on already known guidepost cell populations and will discuss the role of microglia as a potentially new class of atypical guidepost cells.

No MeSH data available.


Related in: MedlinePlus

Microglia in the outgrowth of dopaminergic axons and the positioning of cortical interneurons. (A–C) Schematic representations of coronal hemisections of E14.5 mouse embryonic brain. (D–F) Schematic representations of E18.5 coronal sections through the somatosensory neocortex of mouse embryonic brain. (A) At E14.5, microglia (red) establish a contact with dopaminergic axons (green) entering in the ventral telencephalon. (B) Pharmacologic or genetic cellular ablation (Pu1−∕−), as well as functional impairment (Cx3cr1−∕−) of microglia promote dopaminergic axonal outgrowth in the striatum. (C) Conversely, microglia functional alteration by maternal immune activation (MIA) leads to reduced dopaminergic axonal outgrowth. (D) At E18.5, microglia localize in the deeper layers of the cortical plate, with lhx6-expressing interneurons (gray dots) being concentrated in layer V. (E,F) In absence of microglia (pharmacological depletion or Pu1−∕−) pharmacological immune activation (MIA) or genetic functional alteration of microglia (Dap12−∕−; Cx3cr1−∕−), lhx6-expressing interneurons prematurely entered the cortical plate, followed by an altered laminar distribution. DA, dopaminergic axons; INs, interneurons; IZ, intermediate zone; LGE, lateral ganglionic eminence; MGE, medial ganglionic eminence; Ncx, neocortex; UL, upper layers.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4505395&req=5

Figure 4: Microglia in the outgrowth of dopaminergic axons and the positioning of cortical interneurons. (A–C) Schematic representations of coronal hemisections of E14.5 mouse embryonic brain. (D–F) Schematic representations of E18.5 coronal sections through the somatosensory neocortex of mouse embryonic brain. (A) At E14.5, microglia (red) establish a contact with dopaminergic axons (green) entering in the ventral telencephalon. (B) Pharmacologic or genetic cellular ablation (Pu1−∕−), as well as functional impairment (Cx3cr1−∕−) of microglia promote dopaminergic axonal outgrowth in the striatum. (C) Conversely, microglia functional alteration by maternal immune activation (MIA) leads to reduced dopaminergic axonal outgrowth. (D) At E18.5, microglia localize in the deeper layers of the cortical plate, with lhx6-expressing interneurons (gray dots) being concentrated in layer V. (E,F) In absence of microglia (pharmacological depletion or Pu1−∕−) pharmacological immune activation (MIA) or genetic functional alteration of microglia (Dap12−∕−; Cx3cr1−∕−), lhx6-expressing interneurons prematurely entered the cortical plate, followed by an altered laminar distribution. DA, dopaminergic axons; INs, interneurons; IZ, intermediate zone; LGE, lateral ganglionic eminence; MGE, medial ganglionic eminence; Ncx, neocortex; UL, upper layers.

Mentions: Pharmacologic or genetic ablations of microglia have been used to probe the roles of these cells during embryonic brain wiring (Figure 4). Together with maternal immune activation (MIA) and genetic microglial impairment (Cx3cr1−∕−), these studies showed that microglia regulate the outgrowth of dopaminergic axons, thereby revealing the importance of the precise spatial-temporal microglia localisation (Squarzoni et al., 2014). In addition, microglia contribute to the development of the Corpus Callosum (CC), the largest commissural structure between the cerebral hemispheres (Pont-Lezica et al., 2014). Indeed, genetic functional impairment of microglia (Dap12−∕−) or developmental functional alteration by MIA, down-regulate the expression of genes related to neuritogenesis in microglia, with a consequent impairment on the CC fasciculation in these mouse models. A similar CC fasciculation phenotype has been equally observed in the genetic model of microglia ablation, Pu·1−∕− (Pont-Lezica et al., 2014). Together these studies suggest that the spatial and temporal positioning of embryonic microglia modulates the development of specific and important axonal tracts. The underlying cellular and molecular mechanisms still remain to be deciphered.


Neuronal and microglial regulators of cortical wiring: usual and novel guideposts.

Squarzoni P, Thion MS, Garel S - Front Neurosci (2015)

Microglia in the outgrowth of dopaminergic axons and the positioning of cortical interneurons. (A–C) Schematic representations of coronal hemisections of E14.5 mouse embryonic brain. (D–F) Schematic representations of E18.5 coronal sections through the somatosensory neocortex of mouse embryonic brain. (A) At E14.5, microglia (red) establish a contact with dopaminergic axons (green) entering in the ventral telencephalon. (B) Pharmacologic or genetic cellular ablation (Pu1−∕−), as well as functional impairment (Cx3cr1−∕−) of microglia promote dopaminergic axonal outgrowth in the striatum. (C) Conversely, microglia functional alteration by maternal immune activation (MIA) leads to reduced dopaminergic axonal outgrowth. (D) At E18.5, microglia localize in the deeper layers of the cortical plate, with lhx6-expressing interneurons (gray dots) being concentrated in layer V. (E,F) In absence of microglia (pharmacological depletion or Pu1−∕−) pharmacological immune activation (MIA) or genetic functional alteration of microglia (Dap12−∕−; Cx3cr1−∕−), lhx6-expressing interneurons prematurely entered the cortical plate, followed by an altered laminar distribution. DA, dopaminergic axons; INs, interneurons; IZ, intermediate zone; LGE, lateral ganglionic eminence; MGE, medial ganglionic eminence; Ncx, neocortex; UL, upper layers.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4505395&req=5

Figure 4: Microglia in the outgrowth of dopaminergic axons and the positioning of cortical interneurons. (A–C) Schematic representations of coronal hemisections of E14.5 mouse embryonic brain. (D–F) Schematic representations of E18.5 coronal sections through the somatosensory neocortex of mouse embryonic brain. (A) At E14.5, microglia (red) establish a contact with dopaminergic axons (green) entering in the ventral telencephalon. (B) Pharmacologic or genetic cellular ablation (Pu1−∕−), as well as functional impairment (Cx3cr1−∕−) of microglia promote dopaminergic axonal outgrowth in the striatum. (C) Conversely, microglia functional alteration by maternal immune activation (MIA) leads to reduced dopaminergic axonal outgrowth. (D) At E18.5, microglia localize in the deeper layers of the cortical plate, with lhx6-expressing interneurons (gray dots) being concentrated in layer V. (E,F) In absence of microglia (pharmacological depletion or Pu1−∕−) pharmacological immune activation (MIA) or genetic functional alteration of microglia (Dap12−∕−; Cx3cr1−∕−), lhx6-expressing interneurons prematurely entered the cortical plate, followed by an altered laminar distribution. DA, dopaminergic axons; INs, interneurons; IZ, intermediate zone; LGE, lateral ganglionic eminence; MGE, medial ganglionic eminence; Ncx, neocortex; UL, upper layers.
Mentions: Pharmacologic or genetic ablations of microglia have been used to probe the roles of these cells during embryonic brain wiring (Figure 4). Together with maternal immune activation (MIA) and genetic microglial impairment (Cx3cr1−∕−), these studies showed that microglia regulate the outgrowth of dopaminergic axons, thereby revealing the importance of the precise spatial-temporal microglia localisation (Squarzoni et al., 2014). In addition, microglia contribute to the development of the Corpus Callosum (CC), the largest commissural structure between the cerebral hemispheres (Pont-Lezica et al., 2014). Indeed, genetic functional impairment of microglia (Dap12−∕−) or developmental functional alteration by MIA, down-regulate the expression of genes related to neuritogenesis in microglia, with a consequent impairment on the CC fasciculation in these mouse models. A similar CC fasciculation phenotype has been equally observed in the genetic model of microglia ablation, Pu·1−∕− (Pont-Lezica et al., 2014). Together these studies suggest that the spatial and temporal positioning of embryonic microglia modulates the development of specific and important axonal tracts. The underlying cellular and molecular mechanisms still remain to be deciphered.

Bottom Line: In the last decades, tangential migrating neurons have also been found to participate in the guidance of principal axonal tracts in the forebrain.We furthermore found that microglia participate to the shaping of prenatal forebrain circuits, thereby opening novel perspectives on forebrain development and wiring.Here we will review the last findings on already known guidepost cell populations and will discuss the role of microglia as a potentially new class of atypical guidepost cells.

View Article: PubMed Central - PubMed

Affiliation: Centre National de la Recherche Scientifique UMR8197, Ecole Normale Supérieure, Institut de Biologie, Institut National de la Santé et de la Recherche Médicale U1024 Paris, France.

ABSTRACT
Neocortex functioning relies on the formation of complex networks that begin to be assembled during embryogenesis by highly stereotyped processes of cell migration and axonal navigation. The guidance of cells and axons is driven by extracellular cues, released along by final targets or intermediate targets located along specific pathways. In particular, guidepost cells, originally described in the grasshopper, are considered discrete, specialized cell populations located at crucial decision points along axonal trajectories that regulate tract formation. These cells are usually early-born, transient and act at short-range or via cell-cell contact. The vast majority of guidepost cells initially identified were glial cells, which play a role in the formation of important axonal tracts in the forebrain, such as the corpus callosum, anterior, and post-optic commissures as well as optic chiasm. In the last decades, tangential migrating neurons have also been found to participate in the guidance of principal axonal tracts in the forebrain. This is the case for several examples such as guideposts for the lateral olfactory tract (LOT), corridor cells, which open an internal path for thalamo-cortical axons and Cajal-Retzius cells that have been involved in the formation of the entorhino-hippocampal connections. More recently, microglia, the resident macrophages of the brain, were specifically observed at the crossroads of important neuronal migratory routes and axonal tract pathways during forebrain development. We furthermore found that microglia participate to the shaping of prenatal forebrain circuits, thereby opening novel perspectives on forebrain development and wiring. Here we will review the last findings on already known guidepost cell populations and will discuss the role of microglia as a potentially new class of atypical guidepost cells.

No MeSH data available.


Related in: MedlinePlus