一般口演
神経発生とグリア発生 1
Neurogenesis and Gliogenesis 1
座長：川内 健史（公益財団法人神戸医療産業都市推進機構） |
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| 2022年7月1日 14:00～14:15 ラグナガーデンホテル 羽衣：西 第10会場
2O10a1-01
ラジアルグリア細胞の仮足端におけるグリコーゲン顆粒の分布とリソソームを介した代謝機構の解析
Localization of glycogen granules in the radial glial endfeet and their metabolism through lysosomal degradation regulates radial glial cell differentiation
*後藤 仁志(1)、野村 真(1)、齋藤 成(2,3)、松本 真美(3,4)、大野 伸彦(5,6)、小野 勝彦(1)
1. 京都府立医科大学大学院医学研究科 神経発生生物学、2. 藤田医科大学 医学部 解剖学II 、3. 生理学研究所 電子顕微鏡室、4. 名古屋市立大学 脳神経科学研究所 神経発達再生医学分野、5. 自治医科大学解剖学講座組織学部門、6. 生理学研究所 超微形態研究部門
*Hitoshi Gotoh(1), Tadashi Nomura(1), Sei Saitoh(2,3), Mami Matsumoto(3,4), Nobuhiko Ohno(5,6), Katsuhiko Ono(1)
1. Dept of Biology, Kyoto Pref Univ of Med, Kyoto, Japan, 2. Dept Anat II, Fujita Health Univ, Sch Med, Aichi, Japan, 3. Sec Electron Microsco, Supportive for Brain Research, Nat Inst for Phys Sci, Okazaki, Japan, 4. Dept Dev Reg Neurobiol, Inst Brain Sci, Nagoya City Univ Grad Sch Med Sci, 5. Dept Anat, Div Histol Cell Biol, Jichi Med Univ Sch Med, Tochigi, Japan., 6. Div Ultrastr Res, Nat Inst for Phys Sci, Okazaki, Japan
Keyword: Development, Cortex, Metabolism, Neural stem cell
During mammalian cortical development, radial glial cells (RGCs) act as neural stem cells that generate enormous number of neurons and glial cells. Recently, it was reported that cellular metabolism is an important mechanism to regulate stem cell proliferation or differentiation. In the embryonic cortex, radial glial cells have abundant glycogen granules and elongated mitochondria, suggesting that these components support the radial glial metabolism to regulate the stem cell characteristics. However, functional relevance of these cellular components to the regulation of RGC characteristics remains to be elucidated. . In the present study, we first addressed precise localization of metabolism-related cellular components in E15.5 cortical RGCs by using serial block face scanning electron microscopy. We found accumulation of elongated mitochondoria in both cell bodies and distal endfeet of cortical RGCs, while preferential localization of glycogen granules in distal endfeet as compared to the cell bodies. The majority of glycogen granules were freely distributed throughout the endfeet, and we observed some glycogen granules were surrounded by the double membrane autophagosome-like structure, suggesting that glycogen degradation (glycgogenolysis) occurs in distal endfeet via autophagosome-lysosomal pathway. To examine the role of glycogenolysis in RGCs, we performed functional blocking of acid alpha-glucosidase (GAA), an essential enzyme for lysosomal degradation of glycogen. GAA inhibitor did not affect glycogen amounts in cultured neural progenitor cells under proliferative condition, while it significantly increased glycogen storage and suppressed neuronal production under growth factor-free differentiation condition. To further confirm the role of glycogenolysis in neuronal differentiation, we introduced shRNA expressing vector targeting GAA into cortical RGCs by in utero electroporation. Compared to controls, shRNA against GAA significantly reduced neuronal differentiation and maintained Sox2-positive RGCs in the developing mouse neocortex. Taken altogether, these results suggest that distal endfeet play a significant role in glycogenolysis in RGCs, which is important for active metabolsim and the face decision of RGCs in the developing mammalian neocortex. | | 2022年7月1日 14:15～14:30 ラグナガーデンホテル 羽衣：西 第10会場
2O10a1-02
Development of microcolumns based on radial glial fibers during corticogenesis
*Min Zhang(1), Hisato Maruoka(1), Shigeo Okabe(1)
1. University of Tokyo, Tokyo, Japan
Keyword: microcolumn, subcerebral projection neurons, radial glial fibers, corticogenesis
The mammalian neocortex is comprised of diverse types of neurons. Previous research suggests that subcerebral projection neurons (SCPNs), a primary type of layer 5 excitatory neurons, are organized into a columnar structure perpendicular to the brain surface. This cytoarchitecture is called microcolumns, present in multiple neocortical regions. Microcolumns are arranged as a 2D hexagonal lattice tangential to the brain surface. Each SCPN-microcolumn operates as a functional unit in the adult neocortex, receiving strong common inputs and exhibiting similar stimulus-responsive and synchronous activity. Although microcolumns exist and function in postnatal mice, their development in the embryonic neocortex remains unclear.
Here we revealed that coarse microcolumns are already present at embryonic day 17.5 (E17.5) when SCPNs have completed their radial migration. Because excitatory neurons newly generated from radial glial cells migrate along radial fibers, SCPNs may migrate along specific radial fibers to reach their destination. To test if SCPNs show preference to specific radial fibers, we conducted in utero electroporation to label radial fibers, followed by immunohistochemical labeling of SCPNs. Analysis of spatial relationship between radial fibers and SCPNs suggested that SCPNs were likely to adhere to a subset of radial fibers. This result is consistent with the idea that a subtype of newborn excitatory neurons selects a particular subset of radial fibers for their migration. This model may partially explain the microcolumn formation and imply the heterogeneity of radial glial cells. Our study could provide new insight into a precise mechanism of neocortical development. | | 2022年7月1日 14:30～14:45 ラグナガーデンホテル 羽衣：西 第10会場
2O10a1-03
大脳皮質グリア細胞分化におけるゴルジ体の関与
A possible interaction between the Golgi apparatus and gliogenesis in the developing neocortex
*大石 康二(1,2)、元山 純(3)、仲嶋 一範(2)
1. 同志社大学研究開発推進機構、2. 慶應義塾大学医学部解剖学、3. 同志社大学脳科学研究科
*Koji Oishi(1,2), Jun Motoyama(3), Kazunori Nakajima(2)
1. Org for R&D, Doshisha Univ, Kyoto, Japan, 2. Dept of Anat, Keio Univ Sch of Med, Tokyo, Japan, 3. Grad Sch Brain Science, Doshisha Univ, Kyoto, Japan
Keyword: gliogenesis, Golgi apparatus, stress response, neocortical development
Almost all cells that comprise the mammalian cerebral cortex (neocortex) are generated from common progenitor cells, neural stem/progenitor cells (NSCs or NPCs). The produced cells include a number of different subtypes of neurons and glial cells such as astrocytes and oligodendrocytes, which support neurons in the neural network. As much attention has been paid to understanding function and developmental processes of neurons, which play a central role in the neural network, a wide variety of evidence has been provided so far. On the other hand, recent studies also have provided evidence of the diverse functions of glial cells. In particular, astrocytes, which were considered to just provide survival support on neurons, have been shown to play many important roles in the nervous system by such as recycling neurotransmitters, releasing trophic factors, controlling synaptogenesis and others. However, our understanding on specification and maturation of glial cells during development is currently quite limited.
We recently found that several proteins that are expressed in the Golgi apparatus were involved in gliogenesis. Knockdown of these proteins in NPCs at neurogenic stages resulted in the appearance of glial cells including astrocytes and oligodendrocytes at postnatal stages, as opposed to control knockdown. The structure of the Golgi apparatus in the knockdown cells appeared to be disorganized, suggesting that these cells might have received Golgi stress. Moreover, induction of Golgi stress by another method resulted in the appearance of glial cells. These results support the notion that the Golgi stress response plays an important role in glial cell differentiation from NPCs. We would like to discuss further mechanisms of gliogenesis on the basis of our preliminary results. | | 2022年7月1日 14:45～15:00 ラグナガーデンホテル 羽衣：西 第10会場
2O10a1-04
FGFシグナルのポジティブフィードバックループがアストロサイトの増加と大脳の脳回形成を誘導する
A positive feedback loop of FGF signaling induces astrocyte expansion and folding of the cerebral cortex in gyrencephalic animals
*新明 洋平(1)、齋藤 健吾(1)、浜辺-堀池 俊秀(1)、亀谷 匠郁(1)、服部 剛志(2)、観音 隆幸(3)、細道 一善(3)、Michal Slezak(4)、Matthew G. Holt(4)、田嶋 敦(3)、堀 修(2)、河﨑 洋志(1)
1. 金沢大院医脳神経医学、2. 金沢大院医神経解剖学、3. 金沢大院医革新ゲノム情報学
*Yohei Shinmyo(1), Kengo Saito(1), Toshihide Hamabe-Horiike(1), Narufumi Kameya(1), Tsuyoshi Hattori(2), Takayuki Kannon(3), Kazuyoshi Hosomichi(3), Michal Slezak(4), Matthew G. Holt(4), Atsushi Tajima(3), Osamu Hori(2), Hiroshi Kawasaki(1)
1. Dept. of Med. Neurosci., Grad. Sch. of Med., Kanazawa Univ., Ishikawa, Japan, 2. Dept. of Med. Neuroanat., Grad. Sch. of Med., Kanazawa Univ., Ishikawa, Japan, 3. Dept. of Bioinform. and Genom., Grad. Sch. of Adv. Prev. Med. Sci., Kanazawa Univ., Ishikawa, Japan , 4. VIB Center for Brain and Dis. Res., Leuven, Belgium
Keyword: Astrocyte, Cortical folding, FGF signaling, ferret
During mammalian evolution, the cerebral cortex has changed drastically, resulting in the acquisition of higher cognitive functions. Although notable changes during evolution include the expansion and folding (i.e. gyrification) of the cerebral cortex, and increases in both neurons and astrocytes in the cerebral cortex, the mechanisms and interrelationships among them remain unclear. We have investigated these mechanisms and interrelationships using gyrencephalic carnivore ferrets. Here we show that fibroblast growth factors (FGFs) secreted from ferret astrocytes control the number of astrocytes in an autocrine manner. Interestingly, increasing astrocyte number by activation of FGF signaling induced gyrus-like protrusions in the mouse cerebral cortex. Furthermore, we established genetic manipulation techniques for astrocytes in the ferret cerebral cortex by combining in utero electroporation and the piggyBac system and found that a marked expansion of astrocytes in restricted areas within gyri in the ferret cortex was mediated by a positive feedback loop driven by FGF signaling. Importantly, reduction of astrocytes in the ferret cerebral cortex inhibited cortical folding by suppressing vertical expansion of deep pallial regions in gyri. These results suggest that localized astrogenesis by a positive-feedback loop of FGF signaling is indispensable for cortical folding in the ferret brain via its role in the vertical expansion of the deep pallial regions. Our findings reveal both the cellular mechanisms and the mechanical principle of gyrification in the mammalian cerebral cortex. | |
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