title: Layer V cortical neurons require microglial support for survival during postnatal development.
abstract: Neurons require trophic support during neural circuit formation; however, how the cellular milieu contributes to neuronal survival remains unclear. We found that layer V cortical neurons require support from microglia for survival during postnatal development. Specifically, we found that microglia accumulated close to the subcerebral and callosal projection axons in the postnatal brain. Inactivation of microglia by minocycline treatment or transient ablation of microglia in CD11b-DTR transgenic mice led to increased apoptosis, specifically in layer V subcerebral and callosal projection neurons. CX3CR1 in microglia was required for the survival of layer V neurons. Microglia consistently promoted the survival of cortical neurons in vitro. In addition, we identified microglia-derived IGF1 as a trophic factor that maintained neuronal survival. Our results highlight a neuron-glia interaction that is indispensable for network formation during a specific period in the developing brain.
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Osaka, Japan. ms-ueno@umin.ac.jp
authors.forename: Masaki
authors.initials: M
authors.lastname: Ueno
authors.forename: Yuki
authors.initials: Y
authors.lastname: Fujita
authors.forename: Tatsuhide
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yuka
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Junichi
authors.initials: J
authors.lastname: Kikuta
authors.forename: Masaru
authors.initials: M
authors.lastname: Ishii
authors.forename: Toshihide
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D039481:CD11b Antigen / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D002135:Calcium-Binding Proteins / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D018920:Coculture Techniques; D004167:Diphtheria Toxin / Q000494:pharmacology; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D019707:Receptors, Chemokine / Q000172:deficiency; D014793:Visual Cortex / Q000166:cytology / Q000196:embryology / Q000254:growth & development
chemical_list: C491049:Aif1 protein, mouse; D039481:CD11b Antigen; D000073883:CX3C Chemokine Receptor 1; D002135:Calcium-Binding Proteins; C471885:Cx3cr1 protein, mouse; D004167:Diphtheria Toxin; D004791:Enzyme Inhibitors; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D019707:Receptors, Chemokine; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C517671:Camk2a protein, mouse