Related Experiment Video
Updated: Jul 3, 2026
Assessment of Dendritic Arborization in the Dentate Gyrus of the Hippocampal Region in Mice
Published on: March 31, 2015
Developmental neuronal death in hippocampus requires the microglial CD11b integrin and DAP12 immunoreceptor
Shirley Wakselman1, Catherine Béchade, Anne Roumier
1Laboratoire de Biologie Cellulaire de la Synapse, Institut National de Santé et de Recherche Médicale, Unité 789, 75230 Paris Cedex 05, France.
Abstract:
In several brain regions, microglia actively promote neuronal apoptosis during development. However, molecular actors leading microglia to trigger death remain mostly unknown. Here, we show that, in the developing hippocampus, apoptotic neurons are contacted by microglia expressing both the integrin CD11b and the immunoreceptor DAP12. We demonstrate that developmental apoptosis decreases in mice deficient for CD11b or DAP12. In addition, function-blocking antibodies directed against CD11b decrease neuronal death when injected into wild-type neonates, but have no effect when injected into DAP12-deficient littermates. This demonstrates that DAP12 and CD11b act in converging pathways to induce neuronal death. Finally, we show that DAP12 and CD11b control the production of microglial superoxide ions, which kill the neurons. Thus, our data show that the process of developmental neuronal death triggered by microglia is similar to the elimination of pathogenic cells by the innate immune cells.
Insights
Microglia use CD11b and DAP12 to trigger neuronal apoptosis during development by producing superoxide ions. This process resembles innate immune cells eliminating pathogens.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Microglia, the brain's immune cells, actively induce neuronal apoptosis during development.
- The specific molecular mechanisms by which microglia trigger neuronal death are largely unknown.
Purpose of the Study:
- To identify the molecular players involved in microglial-mediated developmental neuronal apoptosis.
- To elucidate the signaling pathway and mechanism by which microglia induce neuronal death.
Main Methods:
- Investigated microglia-neuron interactions in the developing hippocampus using knockout mice (CD11b and DAP12 deficient).
- Utilized function-blocking antibodies against CD11b in neonatal wild-type and DAP12-deficient mice.
- Assessed microglial superoxide ion production in relation to neuronal apoptosis.
Main Results:
- Apoptotic neurons in the developing hippocampus are contacted by microglia expressing CD11b and DAP12.
- Deficiency in CD11b or DAP12 significantly reduced developmental neuronal apoptosis.
- Antibodies blocking CD11b decreased neuronal death in wild-type but not DAP12-deficient mice, indicating converging pathways.
- CD11b and DAP12 signaling control microglial production of superoxide ions, which mediate neuronal killing.
Conclusions:
- The integrin CD11b and immunoreceptor DAP12 act in a shared pathway to promote developmental neuronal apoptosis.
- Microglia utilize superoxide ions, regulated by CD11b and DAP12, to induce neuronal death.
- Microglial-mediated developmental neuronal apoptosis shares similarities with pathogen elimination by innate immune cells.
