Spatiotemporally Dependent Vascularization Is Differently Utilized among Neural Progenitor Subtypes during Neocortical Development
Mariko Komabayashi-Suzuki,
Emiko Yamanishi,
Chisato Watanabe,
Megumi Okamura,
Hidenori Tabata,
Ryota Iwai,
Itsuki Ajioka,
Jun Matsushita,
Hiroyasu Kidoya,
Nobuyuki Takakura,
Tadashi Okamoto,
Kazuo Kinoshita,
Masamitsu Ichihashi,
Koh-ichi Nagata,
Masatsugu Ema,
Ken-ichi Mizutani
Affiliations
Mariko Komabayashi-Suzuki
Laboratory of Stem Cell Biology, Graduate School of Pharmaceutical Sciences, Kobe Gakuin University, Kobe 650-8586, Japan
Emiko Yamanishi
Graduate School of Brain Science, Doshisha University, Kyoto 619-0225, Japan
Chisato Watanabe
Laboratory of Stem Cell Biology, Graduate School of Pharmaceutical Sciences, Kobe Gakuin University, Kobe 650-8586, Japan; Graduate School of Brain Science, Doshisha University, Kyoto 619-0225, Japan; Department of Stem Cells and Human Disease Models, Research Center for Animal Life Science, Shiga University of Medical Science, Shiga 520-2192, Japan
Megumi Okamura
Laboratory of Stem Cell Biology, Graduate School of Pharmaceutical Sciences, Kobe Gakuin University, Kobe 650-8586, Japan
Hidenori Tabata
Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Developmental Disability Center, Aichi 480-0392, Japan
Ryota Iwai
Laboratory of Stem Cell Biology, Graduate School of Pharmaceutical Sciences, Kobe Gakuin University, Kobe 650-8586, Japan; Graduate School of Brain Science, Doshisha University, Kyoto 619-0225, Japan
Itsuki Ajioka
Center for Brain Integration Research, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
Jun Matsushita
Department of Stem Cells and Human Disease Models, Research Center for Animal Life Science, Shiga University of Medical Science, Shiga 520-2192, Japan
Hiroyasu Kidoya
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
Nobuyuki Takakura
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
Tadashi Okamoto
Laboratory of Biochemistry, Graduate School of Pharmaceutical Sciences, Kobe Gakuin University, Kobe 650-8586, Japan
Kazuo Kinoshita
Shiga Medical Center Research Institute, Shiga 425-8524, Japan
Masamitsu Ichihashi
Laboratory of Biochemistry, Graduate School of Pharmaceutical Sciences, Kobe Gakuin University, Kobe 650-8586, Japan
Koh-ichi Nagata
Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Developmental Disability Center, Aichi 480-0392, Japan
Masatsugu Ema
Department of Stem Cells and Human Disease Models, Research Center for Animal Life Science, Shiga University of Medical Science, Shiga 520-2192, Japan; Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University Institute for Advanced Study, Kyoto 606-8501, Japan
Ken-ichi Mizutani
Laboratory of Stem Cell Biology, Graduate School of Pharmaceutical Sciences, Kobe Gakuin University, Kobe 650-8586, Japan; Graduate School of Brain Science, Doshisha University, Kyoto 619-0225, Japan; PRESTO, Japan Science and Technology Agency, Saitama 332-0012, Japan; Corresponding author
Summary: To facilitate efficient oxygen and nutrient delivery, blood vessels in the brain form three-dimensional patterns. However, little is known about how blood vessels develop stereographically in the neocortex and how they control the expansion and differentiation of neural progenitors during neocortical development. We show that highly vascularized and avascular regions are strictly controlled in a spatially and temporally restricted manner and are associated with distinct cell populations. Dividing basal progenitors and oligodendrocyte precursors preferentially contact honeycomb vessels, but dividing apical progenitors are localized in avascular regions without Flt1-positive endothelial cells but directly contact with sprouting neovascular tip cells. Therefore, not all blood vessels are associated equally with neural progenitors. Furthermore, a disruption of normal vascular patterning can induce abnormalities in neural development, whereas the impaired features of neural progenitors influenced angiogenesis patterning. These results indicate that close association between the nervous and vascular systems is essential for neocortex assembly. : Komabayashi-Suzuki et al. show that regional angiogenesis establishes separate neovascular hypoxic and perivascular niches in the developing neocortex. These niches are utilized by distinct progenitor cell types to achieve proper expansion, lineage specification, and differentiation of neocortical progenitor cells. Keywords: developing neocortex, stem cell niche, neural progenitors, angiogenesis, neurogenesis, VEGF, neural development, differentiation, neural stem cells, oligodendrocyte precursor cells