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Article ; Online: Heterozygous

Honda, Takao / Hirota, Yuki / Nakajima, Kazunori

2023 Volume 10, Issue 4

Abstract: Loss-of-function mutations in Reelin and DAB1 signaling pathways disrupt proper neuronal positioning in the cerebral neocortex and hippocampus, but the underlying molecular mechanisms remain elusive. Here, we report that ... ...

Abstract	Loss-of-function mutations in Reelin and DAB1 signaling pathways disrupt proper neuronal positioning in the cerebral neocortex and hippocampus, but the underlying molecular mechanisms remain elusive. Here, we report that heterozygous
MeSH term(s)	Animals ; Mice ; Hippocampus/metabolism ; Loss of Function Mutation ; Neocortex/metabolism ; Nerve Tissue Proteins/genetics ; Neurons/physiology
Chemical Substances	Dab1 protein, mouse ; Nerve Tissue Proteins
Language	English
Publishing date	2023-04-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2800598-3
ISSN	2373-2822 ; 2373-2822
ISSN (online)	2373-2822
ISSN	2373-2822
DOI	10.1523/ENEURO.0433-22.2023
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Article: Differences in Water Dynamics between the Hydrated Chitin and Hydrated Chitosan Determined by Quasi-Elastic Neutron Scattering.

Hirota, Yuki / Tominaga, Taiki / Kawabata, Takashi / Kawakita, Yukinobu / Matsuo, Yasumitsu

Bioengineering (Basel, Switzerland)

2023 Volume 10, Issue 5

Abstract: Recently, it was reported that chitin and chitosan exhibited high-proton conductivity and function as an electrolyte in fuel cells. In particular, it is noteworthy that proton conductivity in the hydrated chitin becomes 30 times higher than that in the ... ...

Abstract	Recently, it was reported that chitin and chitosan exhibited high-proton conductivity and function as an electrolyte in fuel cells. In particular, it is noteworthy that proton conductivity in the hydrated chitin becomes 30 times higher than that in the hydrated chitosan. Since higher proton conductivity is necessary for the fuel cell electrolyte, it is significantly important to clarify the key factor for the realization of higher proton conduction from a microscopic viewpoint for the future development of fuel cells. Therefore, we have measured proton dynamics in the hydrated chitin using quasi-elastic neutron scattering (QENS) from the microscopic viewpoint and compared the proton conduction mechanism between hydrated chitin and chitosan. QENS results exhibited that a part of hydrogen atoms and hydration water in chitin are mobile even at 238 K, and the mobile hydrogen atoms and their diffusion increase with increasing temperature. It was found that the diffusion constant of mobile protons is two times larger and that the residence time is two times faster in chitin than that in chitosan. In addition, it is revealed from the experimental results that the transition process of dissociable hydrogen atoms between chitin and chitosan is different. To realize proton conduction in the hydrated chitosan, the hydrogen atoms of the hydronium ions (H
Language	English
Publishing date	2023-05-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2746191-9
ISSN	2306-5354
ISSN	2306-5354
DOI	10.3390/bioengineering10050622
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Article ; Online: VLDLR is not essential for reelin-induced neuronal aggregation but suppresses neuronal invasion into the marginal zone.

Hirota, Yuki / Nakajima, Kazunori

Development (Cambridge, England)

2020 Volume 147, Issue 12

Abstract: In the developing neocortex, radially migrating neurons stop migration and form layers beneath the marginal zone (MZ). Reelin plays essential roles in these processes via its receptors, apolipoprotein E receptor 2 (ApoER2) and very low density ... ...

Abstract	In the developing neocortex, radially migrating neurons stop migration and form layers beneath the marginal zone (MZ). Reelin plays essential roles in these processes via its receptors, apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (VLDLR). Although we recently reported that reelin causes neuronal aggregation via ApoER2, which is thought to be important for the subsequent layer formation, it remains unknown what effect reelin exerts via the VLDLR. Here, we found that ectopic reelin overexpression in the
MeSH term(s)	Animals ; Cell Adhesion Molecules, Neuronal/genetics ; Cell Adhesion Molecules, Neuronal/metabolism ; Cerebral Cortex/metabolism ; Dendrites/metabolism ; Embryo, Mammalian/metabolism ; Extracellular Matrix Proteins/genetics ; Extracellular Matrix Proteins/metabolism ; Integrin alpha5/metabolism ; LDL-Receptor Related Proteins/deficiency ; LDL-Receptor Related Proteins/genetics ; Mice ; Mice, Knockout ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Neurons/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Pyramidal Cells/metabolism ; Receptors, LDL/deficiency ; Receptors, LDL/genetics ; Receptors, LDL/metabolism ; Serine Endopeptidases/genetics ; Serine Endopeptidases/metabolism ; rap1 GTP-Binding Proteins/metabolism
Chemical Substances	Cell Adhesion Molecules, Neuronal ; Extracellular Matrix Proteins ; Integrin alpha5 ; LDL-Receptor Related Proteins ; Nerve Tissue Proteins ; Receptors, LDL ; VLDL receptor ; low density lipoprotein receptor-related protein 8 ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Serine Endopeptidases (EC 3.4.21.-) ; reelin protein (EC 3.4.21.-) ; rap1 GTP-Binding Proteins (EC 3.6.5.2)
Language	English
Publishing date	2020-06-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.189936
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Article: Hydrogen Dynamics in Hydrated Chitosan by Quasi-Elastic Neutron Scattering.

Hirota, Yuki / Tominaga, Taiki / Kawabata, Takashi / Kawakita, Yukinobu / Matsuo, Yasumitsu

Bioengineering (Basel, Switzerland)

2022 Volume 9, Issue 10

Abstract: Chitosan, an environmentally friendly and highly bio-producible material, is a potential proton-conducting electrolyte for use in fuel cells. Thus, to microscopically elucidate proton transport in hydrated chitosan, we employed the quasi-elastic neutron ... ...

Abstract	Chitosan, an environmentally friendly and highly bio-producible material, is a potential proton-conducting electrolyte for use in fuel cells. Thus, to microscopically elucidate proton transport in hydrated chitosan, we employed the quasi-elastic neutron scattering (QENS) technique. QENS analysis showed that the hydration water, which was mobile even at 238 K, moved significantly more slowly than the bulk water, in addition to exhibiting jump diffusion. Furthermore, upon increasing the temperature from 238 to 283 K, the diffusion constant of water increased from 1.33 × 10
Language	English
Publishing date	2022-10-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2746191-9
ISSN	2306-5354
ISSN	2306-5354
DOI	10.3390/bioengineering9100599
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Article: Editorial: The Extracellular Environment in Controlling Neuronal Migration During Neocortical Development.

Hirota, Yuki / Ohtaka-Maruyama, Chiaki / Borrell, Victor

Frontiers in cell and developmental biology

2021 Volume 9, Page(s) 673825

Language	English
Publishing date	2021-04-29
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2021.673825
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Article ; Online: A Unique "Reversed" Migration of Neurons in the Developing Claustrum.

Oshima, Kota / Yoshinaga, Satoshi / Kitazawa, Ayako / Hirota, Yuki / Nakajima, Kazunori / Kubo, Ken-Ichiro

The Journal of neuroscience : the official journal of the Society for Neuroscience

2023 Volume 43, Issue 5, Page(s) 693–708

Abstract: The claustrum (CLA) is a cluster of neurons located between the insular cortex and striatum. Many studies have shown that the CLA plays an important role in higher brain function. Additionally, growing evidence suggests that CLA dysfunction is associated ...

Abstract	The claustrum (CLA) is a cluster of neurons located between the insular cortex and striatum. Many studies have shown that the CLA plays an important role in higher brain function. Additionally, growing evidence suggests that CLA dysfunction is associated with neuropsychological symptoms. However, how the CLA is formed during development is not fully understood. In the present study, we analyzed the development of the CLA, especially focusing on the migration profiles of CLA neurons in mice of both sexes. First, we showed that CLA neurons were generated between embryonic day (E) 10.5 and E12.5, but mostly at E11.5. Next, we labeled CLA neurons born at E11.5 using the FlashTag technology and revealed that most neurons reached the brain surface by E13.5 but were distributed deep in the CLA 1 d later at E14.5. Time-lapse imaging of GFP-labeled cells revealed that some CLA neurons first migrated radially outward and then changed their direction inward after reaching the surface. Moreover, we demonstrated that Reelin signal is necessary for the appropriate distribution of CLA neurons. The switch from outward to "reversed" migration of developing CLA neurons is distinct from other migration modes, in which neurons typically migrate in a certain direction, which is simply outward or inward. Future elucidation of the characteristics and precise molecular mechanisms of CLA development may provide insights into the unique cognitive functions of the CLA.
MeSH term(s)	Female ; Male ; Mice ; Animals ; Claustrum/physiology ; Neurons/physiology ; Cell Movement/physiology ; Corpus Striatum ; Neurogenesis
Language	English
Publishing date	2023-01-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.0704-22.2022
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Article: Control of Neuronal Migration and Aggregation by Reelin Signaling in the Developing Cerebral Cortex.

Hirota, Yuki / Nakajima, Kazunori

Frontiers in cell and developmental biology

2017 Volume 5, Page(s) 40

Abstract: The mammalian cerebral neocortex has a well-organized laminar structure, achieved by the highly coordinated control of neuronal migration. During cortical development, excitatory neurons born near the lateral ventricle migrate radially to reach their ... ...

Abstract	The mammalian cerebral neocortex has a well-organized laminar structure, achieved by the highly coordinated control of neuronal migration. During cortical development, excitatory neurons born near the lateral ventricle migrate radially to reach their final positions to form the cortical plate. During this process, dynamic changes are observed in the morphologies and migration modes, including multipolar migration, locomotion, and terminal translocation, of the newborn neurons. Disruption of these migration processes can result in neuronal disorders such as lissencephaly and periventricular heterotopia. The extracellular protein, Reelin, mainly secreted by the Cajal-Retzius neurons in the marginal zone during development, plays a crucial role in the neuronal migration and neocortical lamination. Reelin signaling, which exerts essential roles in the formation of the layered neocortex, is triggered by the binding of Reelin to its receptors, ApoER2 and VLDLR, followed by phosphorylation of the Dab1 adaptor protein. Accumulating evidence suggests that Reelin signaling controls multiple steps of neuronal migration, including the transition from multipolar to bipolar neurons, terminal translocation, and termination of migration beneath the marginal zone. In addition, it has been shown that ectopically expressed Reelin can cause neuronal aggregation via an N-cadherin-mediated manner. This review attempts to summarize our knowledge of the roles played by Reelin in neuronal migration and the underlying mechanisms.
Language	English
Publishing date	2017-04-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2017.00040
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Article ; Online: The Secreted Glycoprotein Reelin Suppresses the Proliferation and Regulates the Distribution of Oligodendrocyte Progenitor Cells in the Embryonic Neocortex.

Ogino, Himari / Nakajima, Tsuzumi / Hirota, Yuki / Toriuchi, Kohki / Aoyama, Mineyoshi / Nakajima, Kazunori / Hattori, Mitsuharu

The Journal of neuroscience : the official journal of the Society for Neuroscience

2020 Volume 40, Issue 40, Page(s) 7625–7636

Abstract: Oligodendrocyte (OL) progenitor cells (OPCs) are generated, proliferate, migrate, and differentiate in the developing brain. Although the development of OPCs is prerequisite for normal brain function, the molecular mechanisms regulating their development ...

Abstract	Oligodendrocyte (OL) progenitor cells (OPCs) are generated, proliferate, migrate, and differentiate in the developing brain. Although the development of OPCs is prerequisite for normal brain function, the molecular mechanisms regulating their development in the neocortex are not fully understood. Several molecules regulate the tangential distribution of OPCs in the developing neocortex, but the cue molecule(s) that regulate their radial distribution remains unknown. Here, we demonstrate that the secreted glycoprotein Reelin suppresses the proliferation of OPCs and acts as a repellent for their migration
MeSH term(s)	ADAMTS Proteins/metabolism ; Animals ; Cell Adhesion Molecules, Neuronal/genetics ; Cell Adhesion Molecules, Neuronal/metabolism ; Cells, Cultured ; Extracellular Matrix Proteins/genetics ; Extracellular Matrix Proteins/metabolism ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Neocortex/cytology ; Neocortex/embryology ; Neocortex/metabolism ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Neural Stem Cells/cytology ; Neural Stem Cells/metabolism ; Neurogenesis ; Oligodendroglia/cytology ; Oligodendroglia/metabolism ; Protein Binding ; Receptors, LDL/metabolism ; Serine Endopeptidases/genetics ; Serine Endopeptidases/metabolism
Chemical Substances	Cell Adhesion Molecules, Neuronal ; Dab1 protein, mouse ; Extracellular Matrix Proteins ; Nerve Tissue Proteins ; Receptors, LDL ; VLDL receptor ; Serine Endopeptidases (EC 3.4.21.-) ; reelin protein (EC 3.4.21.-) ; ADAMTS Proteins (EC 3.4.24.-) ; Adamts3 protein, mouse (EC 3.4.24.-)
Language	English
Publishing date	2020-09-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.0125-20.2020
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Article ; Online: TPT1 Supports Proliferation of Neural Stem/Progenitor Cells and Brain Tumor Initiating Cells Regulated by Macrophage Migration Inhibitory Factor (MIF).

Morimoto, Yukina / Tokumitsu, Ayako / Sone, Takefumi / Hirota, Yuki / Tamura, Ryota / Sakamoto, Ayuna / Nakajima, Kazunori / Toda, Masahiro / Kawakami, Yutaka / Okano, Hideyuki / Ohta, Shigeki

Neurochemical research

2022 Volume 47, Issue 9, Page(s) 2741–2756

Abstract: One of the key areas in stem cell research is the identification of factors capable of promoting the expansion of Neural Stem Cell/Progenitor Cells (NSPCs) and understanding their molecular mechanisms for future use in clinical settings. We previously ... ...

Abstract	One of the key areas in stem cell research is the identification of factors capable of promoting the expansion of Neural Stem Cell/Progenitor Cells (NSPCs) and understanding their molecular mechanisms for future use in clinical settings. We previously identified Macrophage Migration Inhibitory Factor (MIF) as a novel factor that can support the proliferation and/or survival of NSPCs based on in vitro functional cloning strategy and revealed that MIF can support the proliferation of human brain tumor-initiating cells (BTICs). However, the detailed downstream signaling for the functions has largely remained unknown. Thus, in the present study, we newly identified translationally-controlled tumor protein-1 (TPT1), which is expressed in the ventricular zone of mouse embryonic brain, as a downstream target of MIF signaling in mouse and human NSPCs and human BTICs. Using gene manipulation (over or downregulation of TPT1) techniques including CRISPR/Cas9-mediated heterozygous gene disruption showed that TPT1 contributed to the regulation of cell proliferation/survival in mouse NSPCs, human embryonic stem cell (hESC) derived-NSPCs, human-induced pluripotent stem cells (hiPSCs) derived-NSPCs and BTICs. Furthermore, gene silencing of TPT1 caused defects in neuronal differentiation in the NSPCs in vitro. We also identified the MIF-CHD7-TPT1-SMO signaling axis in regulating hESC-NSPCs and BTICs proliferation. Intriguingly, TPT1suppressed the miR-338 gene, which targets SMO in hESC-NSPCs and BTICs. Finally, mice with implanted BTICs infected with lentivirus-TPT1 shRNA showed a longer overall survival than control. These results also open up new avenues for the development of glioma therapies based on the TPT1 signaling pathway.
MeSH term(s)	Animals ; Brain/metabolism ; Cell Proliferation/physiology ; Humans ; Intramolecular Oxidoreductases ; Macrophage Migration-Inhibitory Factors/genetics ; Macrophage Migration-Inhibitory Factors/metabolism ; Mice ; MicroRNAs/metabolism ; Neoplasm Proteins/metabolism ; Neoplastic Stem Cells/metabolism ; Neural Stem Cells/metabolism ; Tumor Protein, Translationally-Controlled 1/genetics
Chemical Substances	Macrophage Migration-Inhibitory Factors ; MicroRNAs ; Neoplasm Proteins ; Tpt1 protein, mouse ; Tumor Protein, Translationally-Controlled 1 ; Intramolecular Oxidoreductases (EC 5.3.-) ; Mif protein, mouse (EC 5.3.2.1)
Language	English
Publishing date	2022-05-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	199335-5
ISSN	1573-6903 ; 0364-3190
ISSN (online)	1573-6903
ISSN	0364-3190
DOI	10.1007/s11064-022-03629-6
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Zs.A 1368: Show issues

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Article ; Online: Reelin-Nrp1 Interaction Regulates Neocortical Dendrite Development in a Context-Specific Manner.

Kohno, Takao / Ishii, Keisuke / Hirota, Yuki / Honda, Takao / Makino, Makoto / Kawasaki, Takahiko / Nakajima, Kazunori / Hattori, Mitsuharu

The Journal of neuroscience : the official journal of the Society for Neuroscience

2020 Volume 40, Issue 43, Page(s) 8248–8261

Abstract: Reelin plays versatile roles in neocortical development. The C-terminal region (CTR) of Reelin is required for the correct formation of the superficial structure of the neocortex; however, the mechanisms by which this position-specific effect occurs ... ...

Abstract	Reelin plays versatile roles in neocortical development. The C-terminal region (CTR) of Reelin is required for the correct formation of the superficial structure of the neocortex; however, the mechanisms by which this position-specific effect occurs remain largely unknown. In this study, we demonstrate that Reelin with an intact CTR binds to neuropilin-1 (Nrp1), a transmembrane protein. Both male and female mice were used. Nrp1 is localized with very-low-density lipoprotein receptor (VLDLR), a canonical Reelin receptor, in the superficial layers of the developing neocortex. It forms a complex with VLDLR, and this interaction is modulated by the alternative splicing of VLDLR. Reelin with an intact CTR binds more strongly to the VLDLR/Nrp1 complex than to VLDLR alone. Knockdown of Nrp1 in neurons leads to the accumulation of Dab1 protein. Since the degradation of Dab1 is induced by Reelin signaling, it is suggested that Nrp1 augments Reelin signaling. The interaction between Reelin and Nrp1 is required for normal dendritic development in superficial-layer neurons. All of these characteristics of Reelin are abrogated by proteolytic processing of the six C-terminal amino acid residues of Reelin (0.17% of the whole protein). Therefore, Nrp1 is a coreceptor molecule for Reelin and, together with the proteolytic processing of Reelin, can account for context-specific Reelin function in brain development.
MeSH term(s)	Animals ; Cell Adhesion Molecules, Neuronal/genetics ; Cell Adhesion Molecules, Neuronal/metabolism ; Cell Line ; DNA/metabolism ; Dendrites/physiology ; Extracellular Matrix Proteins/genetics ; Extracellular Matrix Proteins/metabolism ; Female ; Gene Knockdown Techniques ; Male ; Mice ; Mice, Inbred ICR ; Neocortex/cytology ; Neocortex/growth & development ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Neuropilin-1/genetics ; Neuropilin-1/physiology ; Receptors, LDL/metabolism ; Serine Endopeptidases/genetics ; Serine Endopeptidases/metabolism
Chemical Substances	Cell Adhesion Molecules, Neuronal ; Dab1 protein, mouse ; Extracellular Matrix Proteins ; Nerve Tissue Proteins ; Receptors, LDL ; VLDL receptor ; Neuropilin-1 (144713-63-3) ; DNA (9007-49-2) ; Serine Endopeptidases (EC 3.4.21.-) ; reelin protein (EC 3.4.21.-)
Language	English
Publishing date	2020-10-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.1907-20.2020
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