若手道場
神経・グリアの発生と分化 |
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| 7月6日（木） 14:20-15:20 Room D
1W③-1
分泌型タンパク質Akhirinは脳発生時の自然免疫応答を制御し神経幹細胞ニッチの恒常性の維持に働く
Akhirin Regulates the innate Immune Response During Brain Development and Maintains Homeostasis of the NSC Niche
工藤 三希子1, 大久保 天太1, 松尾 直毅3, 増田 隆博4, 太田 訓正1,2
1. 九州大学 幹細胞生物学, 2. 九州大学基幹教育院, 3. 九州大学 行動神経科学, 4. 九州大学 分子神経免疫学
Mikiko Kudo1, Tenta Ohkubo1, Naoki Matsuo3, Takahiro Masuda4, Kunimasa Ohta1,2
1. Dept. of Stem Cell Biology., Kyushu University, Fukuoka, Japan
Akhirin (AKH) is a novel secretory molecule and exhibits heterophilic cell adhesion property. AKH expressed explicitly in the neural stem cell (NSC) niche region of the central nervous system (CNS), also in eye, spinal cord, and brain. Our findings suggest that AKH plays a crucial role in CNS development, however the detail molecular function of AKH in the developing CNS is still unexplored.Here, using an anti-AKH polyclonal antibody, we have noticed that AKH protein is expressed in the neuronal ependymal cells layer, choroid plexus ependymal cells layer, and the cerebral spinal fluid (CSF) in the mouse embryonic brain. Compared to wild-type mice, AKH knock out mice (AKH-/-) showed aberrant Lateral Ventricle (LV) expansion and suppressed NSC proliferation, as well as behavioral abnormalities. Furthermore, we have observed abnormal vascular formation and the over activation of microglia in the AKH-/- brain. To elucidate the reason behind microglial activation induced by AKH deficiency, we examined whether AKH is involved in the innate immune response in the brain. Here, our observations suggest that AKH is involved in the regulates the innate immunity while maintaining homeostasis of NSC niche during the brain development. | | 7月6日（木） 14:20-15:20 Room D
1W③-2
胎生早期における脳実質侵入時のマクロファージと神経前駆細胞の相互作用
Intraventricular macrophages infiltrate the cerebral wall in association with neural progenitor cells
浅井 日沙, 服部 祐季, 宮田 卓樹
名古屋大学大学院医学系研究科 細胞生物学分野
Hisa Asai, Yuki Hattori, Takaki Miyata
Dept. of Anat. Cell Biol., Grad. Sch. of Med., Nagoya Univ., Nagoya, Japan.
Microglia are the immune cells in the brain. During embryonic development, microglia promote the differentiation into intermediate progenitor cells, maintain the number of intermediate progenitors by phagocytosis, and control the positioning of interneurons migrating from the ganglionic eminence to the cerebral wall. In addition, previous studies based on single-cell RNA analysis demonstrated that microglia are heterogenous population in gene expression pattern. We hypothesized that such functional and gene expression diversities emerge due to the differences in the routes by which microglia migrate and colonize into the brain. As one of the pathways, we recently reported that macrophages in the ventricle of the brain infiltrate the cerebral wall at embryonic day 12 (E12) in mice, and differentiate into microglia in the parenchyma. However, the mechanism by which intraventricular macrophages infiltrate the cerebral wall is still unclear.
To address this, we have investigated the characteristic of the intraventricular macrophages and their relationship with neural progenitor cells, which might be unique phenomenon at E12 in mice.
In my talk, I will report the results of our studies on the interaction between intraventricular macrophages and neural progenitor cells, and the contribution of phagocytic activity of macrophages to their entrance into the cerebra wall. | | 7月6日（木） 14:20-15:20 Room D
1W③-3
プリン代謝による発達期ミクログリアの成熟制御メカニズム
A novel mechanism for microglial maturation mediated by purine metabolisms
照屋 林一郎1, 岡島-高橋 智美1, 上田 健太郎2, 鶴田 文憲3
1. 筑波大学 理工情報生命学術院 生命地球科学研究群 生物学学位プログラム, 2. 筑波大学 生命環境学群 生物学類, 3. 筑波大学 生命環境系
Rin-ichiro Teruya1, Tomomi Okajima-Takahashi1, Kentaro Ueda2, Fuminori Tsuruta3
1. Grad Sch of Life and Env Sci, Univ of Tsukuba, Japan, 2. Col of Biol Sci, Sch of Life and Env, Univ of Tsukuba, Japan, 3. Faculty of Life and Env Sci, Univ of Tsukuba, Japan
Microglia are resident macrophages in the central nervous system. In general, microglial morphology and function are gradually changed and exhibit a highly diversified population during early postnatal stages. However, the mechanisms by which microglia take on heterogeneity developmentally have been insufficiently explored. Here, we report that an increase in the enzymatic activity of hypoxanthine-guanine phosphoribosyltransferase (HPRT) triggers microglial maturation. We found that hypoxanthine stimulation elongates the processes of microglial cell line BV2 in conjunction with HPRT expression. Furthermore, HPRT mutants that lack enzymatic activity do not lead to morphological change. These data highlight that the enzymatic activity of HPRT is crucial for microglial maturation in the developmental stage and suggests that purine metabolism influences actin reorganization. | | 7月6日（木） 14:20-15:20 Room D
1W③-4
Antibody-directed proximity biotinylation reveals Contactin-1 regulates axon initial segment axo-axonic innervation.
小川 優樹1, Brian Lim1, Shanu George1, Juan Oses-Prieto4, Yael Eshed-Eisenbach2, Elior Peles3, Alma Burlingame3, Linda Van-Aelst2, Matthew Rasband4
1. ベイラー医科大学 神経科学, 2. カリフォルニア大学サンフランシスコ校, 3. ワイツマン科学研究所, 4. コールドスプリングハーバー研究所
Yuki Ogawa1, Brian Lim1, Shanu George1, Juan Oses-Prieto4, Yael Eshed-Eisenbach2, Elior Peles3, Alma Burlingame3, Linda Van-Aelst2, Matthew Rasband4
1. Baylor College of Medicine, Dept. of Neuroscience
Axon initial segment (AIS) membrane proteins mediate key biological processes in neurons. For example, AIS Na+ and K+ channels initiate action potentials, while other AIS membrane proteins assemble AIS-specific perineuronal nets and inhibitory synapses. However, relatively few AIS membrane proteins have been reported. Here, using biotinylation by antibody recognition, we report the extracellular Neurofascin proximity proteome across five developmental timepoints. We identified all previously reported AIS cell adhesion molecules and extracellular membrane-associated proteins. We used CRISPR/Cas9 and homology independent genome editing to determine the distributions of membrane proteins in close proximity to Neurofascin. Among these, we found that Contactin-1 is enriched at the AIS and is required to recruit TenascinR to the AIS-extracellular matrix. In addition, we mapped other membrane proteins to axonal, AIS, and dendritic domains. This strategy enables flexible and temporally resolved proteomic profiling as a discovery tool to elucidate the proximity proteomes of surface membrane proteins. | |
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