title: Complex invasion pattern of the cerebral cortex bymicroglial cells during development of the mouse embryo.
abstract: Microglia are the immune cells of the central nervous system. They are suspected to play important roles in adult synaptogenesis and in the development of the neuronal network. Microglial cells originate from progenitors in the yolk sac. Although it was suggested that they invade the cortex at early developmental stages in the embryo, their invasion pattern remains largely unknown. To address this issue we analyzed the pattern of cortical invasion by microglial cells in mouse embryos at the onset of neuronal cell migration using in vivo immunohistochemistry and ex vivo time-lapse analysis of microglial cells. Microglial cells begin to invade the cortex at 11.5 days of embryonic age (E11.5). They first accumulate at the pial surface and within the lateral ventricles, after which they spread throughout the cortical wall, avoiding the cortical plate region in later embryonic ages. The invasion of the cortical parenchyma occurs in different phases. First, there is a gradual increase of microglial cells between E10.5 and E14.5. From E14.5 to E15.5 there is a rapid phase with a massive increase in microglia, followed by a slow phase again from E15.5 until E17.5. At early stages, many peripheral microglia are actively proliferating before entering the parenchyma. Remarkably, activated microglia accumulate in the choroid plexus primordium, where they are in the proximity of dying cells. Time-lapse analysis shows that embryonic microglia are highly dynamic cells.
authors.affiliation: Hasselt University, BIOMED, Agoralaan (Gebouw C), Diepenbeek B-3590, Belgium.
authors.forename: Nina
authors.initials: N
authors.lastname: Swinnen
authors.forename: Sophie
authors.initials: S
authors.lastname: Smolders
authors.forename: Ariel
authors.initials: A
authors.lastname: Avila
authors.forename: Kristof
authors.initials: K
authors.lastname: Notelaers
authors.forename: Rik
authors.initials: R
authors.lastname: Paesen
authors.forename: Marcel
authors.initials: M
authors.lastname: Ameloot
authors.forename: Bert
authors.initials: B
authors.lastname: Brône
authors.forename: Pascal
authors.initials: P
authors.lastname: Legendre
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Rigo
mesh_terms: D000367:Age Factors; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology*; D002831:Choroid Plexus / Q000166:cytology / Q000196:embryology; D004622:Embryo, Mammalian / Q000033:anatomy & histology; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D037502:Galectin 3 / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000502:physiology*; D018613:Microscopy, Confocal; D009474:Neurons / Q000502:physiology; D011247:Pregnancy; D023062:Receptors, Interleukin-8A / Q000235:genetics; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002135:Calcium-Binding Proteins; D053148:Caspase 3; D037502:Galectin 3; D049452:Green Fluorescent Proteins; D019394:Ki-67 Antigen; D008840:Microfilament Proteins; D023062:Receptors, Interleukin-8A; C491049:Aif1 protein, mouse; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C485184:enhanced green fluorescent protein