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Cell biology in neuroscience: Architects in neural circuit design: glia control neuron numbers and connectivity.

Corty MM, Freeman MR - J. Cell Biol. (2013)

Bottom Line: Glia serve many important functions in the mature nervous system.In addition, these diverse cells have emerged as essential participants in nearly all aspects of neural development.Recent findings illustrate the importance of glial cells in shaping the nervous system by controlling the number and connectivity of neurons.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurobiology, University of Massachusetts Medical School, Howard Hughes Medical Institute, Worcester, MA 01605.

ABSTRACT
Glia serve many important functions in the mature nervous system. In addition, these diverse cells have emerged as essential participants in nearly all aspects of neural development. Improved techniques to study neurons in the absence of glia, and to visualize and manipulate glia in vivo, have greatly expanded our knowledge of glial biology and neuron-glia interactions during development. Exciting studies in the last decade have begun to identify the cellular and molecular mechanisms by which glia exert control over neuronal circuit formation. Recent findings illustrate the importance of glial cells in shaping the nervous system by controlling the number and connectivity of neurons.

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Microglia promote cell death and clearance of neuronal debris in the developing brain. (A) Model of the role of microglia in promoting neuronal programmed cell death in the developing cerebellum and hippocampus. Caspase-3+ neurons that have initiated apoptosis express as-yet-unknown “kill me/eat me” signals that recruit microglia to engulf them. Contact between dying neurons and microglia expressing the integrin CD11b and the immunoreceptor DAP12 triggers production of reactive oxygen species (including O2.−) in microglia, which is locally released to promote completion of apoptosis in the dying neuron. CD11b and DAP12 are required in microglia for efficient ROS production and for normal levels of PCD, but it remains unclear whether CD11b/DAP12 act as a receptor for one of the elusive neuronal signal(s), or if other receptors indirectly activate this pathway. (B) Microglia are also required for the clearance of cellular debris generated by PCD. The neuronal signals and specific microglial receptors that mediate corpse recognition and phagocytosis also remain unknown. Proper clearance of corpses is required to prevent inflammation.
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fig1: Microglia promote cell death and clearance of neuronal debris in the developing brain. (A) Model of the role of microglia in promoting neuronal programmed cell death in the developing cerebellum and hippocampus. Caspase-3+ neurons that have initiated apoptosis express as-yet-unknown “kill me/eat me” signals that recruit microglia to engulf them. Contact between dying neurons and microglia expressing the integrin CD11b and the immunoreceptor DAP12 triggers production of reactive oxygen species (including O2.−) in microglia, which is locally released to promote completion of apoptosis in the dying neuron. CD11b and DAP12 are required in microglia for efficient ROS production and for normal levels of PCD, but it remains unclear whether CD11b/DAP12 act as a receptor for one of the elusive neuronal signal(s), or if other receptors indirectly activate this pathway. (B) Microglia are also required for the clearance of cellular debris generated by PCD. The neuronal signals and specific microglial receptors that mediate corpse recognition and phagocytosis also remain unknown. Proper clearance of corpses is required to prevent inflammation.

Mentions: Overproduction, followed by programmed cell death (PCD) of excess neurons, is a well-described and conserved feature of nervous system development across phyla that is designed to ensure a sufficient number of neurons are initially formed to accomplish neural circuit construction (see Dekkers et al., in this issue). Competition between neurons for limited environmental and target-derived trophic factors results in cell death of extraneous or weakly connected neurons (Levi-Montalcini, 1987). PCD most often occurs via apoptosis followed by phagocytosis of the cellular debris by microglia, the resident immune cells and phagocytes of the central nervous system. A number of recent studies in the rodent have challenged the view that microglia act as passive scavengers of cellular debris. Rather, accumulating evidence now demonstrates an active role for microglia and innate immune mechanisms in promoting developmental PCD (Fig. 1).


Cell biology in neuroscience: Architects in neural circuit design: glia control neuron numbers and connectivity.

Corty MM, Freeman MR - J. Cell Biol. (2013)

Microglia promote cell death and clearance of neuronal debris in the developing brain. (A) Model of the role of microglia in promoting neuronal programmed cell death in the developing cerebellum and hippocampus. Caspase-3+ neurons that have initiated apoptosis express as-yet-unknown “kill me/eat me” signals that recruit microglia to engulf them. Contact between dying neurons and microglia expressing the integrin CD11b and the immunoreceptor DAP12 triggers production of reactive oxygen species (including O2.−) in microglia, which is locally released to promote completion of apoptosis in the dying neuron. CD11b and DAP12 are required in microglia for efficient ROS production and for normal levels of PCD, but it remains unclear whether CD11b/DAP12 act as a receptor for one of the elusive neuronal signal(s), or if other receptors indirectly activate this pathway. (B) Microglia are also required for the clearance of cellular debris generated by PCD. The neuronal signals and specific microglial receptors that mediate corpse recognition and phagocytosis also remain unknown. Proper clearance of corpses is required to prevent inflammation.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3824021&req=5

fig1: Microglia promote cell death and clearance of neuronal debris in the developing brain. (A) Model of the role of microglia in promoting neuronal programmed cell death in the developing cerebellum and hippocampus. Caspase-3+ neurons that have initiated apoptosis express as-yet-unknown “kill me/eat me” signals that recruit microglia to engulf them. Contact between dying neurons and microglia expressing the integrin CD11b and the immunoreceptor DAP12 triggers production of reactive oxygen species (including O2.−) in microglia, which is locally released to promote completion of apoptosis in the dying neuron. CD11b and DAP12 are required in microglia for efficient ROS production and for normal levels of PCD, but it remains unclear whether CD11b/DAP12 act as a receptor for one of the elusive neuronal signal(s), or if other receptors indirectly activate this pathway. (B) Microglia are also required for the clearance of cellular debris generated by PCD. The neuronal signals and specific microglial receptors that mediate corpse recognition and phagocytosis also remain unknown. Proper clearance of corpses is required to prevent inflammation.
Mentions: Overproduction, followed by programmed cell death (PCD) of excess neurons, is a well-described and conserved feature of nervous system development across phyla that is designed to ensure a sufficient number of neurons are initially formed to accomplish neural circuit construction (see Dekkers et al., in this issue). Competition between neurons for limited environmental and target-derived trophic factors results in cell death of extraneous or weakly connected neurons (Levi-Montalcini, 1987). PCD most often occurs via apoptosis followed by phagocytosis of the cellular debris by microglia, the resident immune cells and phagocytes of the central nervous system. A number of recent studies in the rodent have challenged the view that microglia act as passive scavengers of cellular debris. Rather, accumulating evidence now demonstrates an active role for microglia and innate immune mechanisms in promoting developmental PCD (Fig. 1).

Bottom Line: Glia serve many important functions in the mature nervous system.In addition, these diverse cells have emerged as essential participants in nearly all aspects of neural development.Recent findings illustrate the importance of glial cells in shaping the nervous system by controlling the number and connectivity of neurons.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurobiology, University of Massachusetts Medical School, Howard Hughes Medical Institute, Worcester, MA 01605.

ABSTRACT
Glia serve many important functions in the mature nervous system. In addition, these diverse cells have emerged as essential participants in nearly all aspects of neural development. Improved techniques to study neurons in the absence of glia, and to visualize and manipulate glia in vivo, have greatly expanded our knowledge of glial biology and neuron-glia interactions during development. Exciting studies in the last decade have begun to identify the cellular and molecular mechanisms by which glia exert control over neuronal circuit formation. Recent findings illustrate the importance of glial cells in shaping the nervous system by controlling the number and connectivity of neurons.

Show MeSH
Related in: MedlinePlus