CD206+ macrophages transventricularly infiltrate the early embryonic cerebral wall to differentiate into microglia
Yuki Hattori,
Daisuke Kato,
Futoshi Murayama,
Sota Koike,
Hisa Asai,
Ayato Yamasaki,
Yu Naito,
Ayano Kawaguchi,
Hiroyuki Konishi,
Marco Prinz,
Takahiro Masuda,
Hiroaki Wake,
Takaki Miyata
Affiliations
Yuki Hattori
Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; Corresponding author
Daisuke Kato
Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Futoshi Murayama
Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Sota Koike
Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Hisa Asai
Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Ayato Yamasaki
Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Yu Naito
Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; Department of Pathology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo 113-8677, Japan
Ayano Kawaguchi
Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; Department of Human Morphology, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama 700-8558, Japan
Hiroyuki Konishi
Department of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Marco Prinz
Institute of Neuropathology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, 79106 Freiburg, Germany
Takahiro Masuda
Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Hiroaki Wake
Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; Department of Physiological Sciences, The Graduate School for Advanced Study, Okazaki 444-0864, Japan; Division of Multicellular Circuit Dynamics, National Institute for Physiological Sciences, National Institute of Natural Sciences, Okazaki 444-8585, Japan; Center of Optical Scattering Image Science, Kobe University, Kobe 657-8501, Japan
Takaki Miyata
Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Summary: The relationships between tissue-resident microglia and early macrophages, especially their lineage segregation outside the yolk sac, have been recently explored, providing a model in which a conversion from macrophages seeds microglia during brain development. However, spatiotemporal evidence to support such microglial seeding in situ and to explain how it occurs has not been obtained. By cell tracking via slice culture, intravital imaging, and Flash tag-mediated or genetic labeling, we find that intraventricular CD206+ macrophages, which are abundantly observed along the inner surface of the mouse cerebral wall, frequently enter the pallium at embryonic day 12. Immunofluorescence of the tracked cells show that postinfiltrative macrophages in the pallium acquire microglial properties while losing the CD206+ macrophage phenotype. We also find that intraventricular macrophages are supplied transepithelially from the roof plate. This study demonstrates that the “roof plate→ventricle→pallium” route is an essential path for microglial colonization into the embryonic mouse brain.
