Article
Cell Biology
Qingyou Li, Nicole K. Morrill, Andrea M. Moerman-Herzog, Steven W. Barger, Aurelie Joly-Amado, Melinda Peters, Hana Soueidan, Cory Diemler, Sahana Prabhudeva, Edwin J. Weeber, Kevin R. Nash
Summary: In this study, a novel cell-based assay using a split-luciferase approach was developed to investigate ApoER2 dimerization. The results showed that ApoER2 receptors can dimerize in transfected cells and the central fragment of reelin can activate intracellular signaling pathways through receptor clustering. Furthermore, the central fragment of reelin was able to rescue phenotypic deficits in heterozygous reeler mice.
CELLULAR SIGNALLING
(2023)
Article
Multidisciplinary Sciences
Ji-Woon Kim, Joachim Herz, Ege T. Kavalali, Lisa M. Monteggia
Summary: This study investigated whether disruptions in Reelin-mediated synaptic signaling alter ketamine-triggered synaptic plasticity and behavioral effects. The findings suggest that impairments in Reelin-Apoer2-SFK pathway components may in part underlie nonresponsiveness to ketamine's antidepressant action.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Xiaoling Xu, Xinmei Lan, Shuhua Fu, Qian Zhang, Fu Gui, Qifang Jin, Lin Xie, Xiong Yu
Summary: This study reveals the involvement of Reelin/DAB1 signaling in the progression of diabetic retinopathy (DR). Increased expression of Reelin, DAB1, and related proteins was observed in a DR mouse model and high glucose-treated human retinal pigment epithelium cells. TRIM40, an E3 ubiquitin ligase, was found to be dysregulated in DR and negatively correlated with p-DAB1 protein expression levels. TRIM40 was shown to promote DAB1 degradation through K48-linked polyubiquitination, thus limiting DAB1 stability. Over-expression of TRIM40 ameliorated DR phenotypes in mice and attenuated inflammation and p-DAB1 expression in retinal tissues.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Neurosciences
Stephane Bugeon, Clara Haubold, Alexandre Ryzynski, Harold Cremer, Jean-Claude Platel
Summary: The study investigates the impact of neuronal activity on the migration of different interneuron subtypes, revealing a significant increase in intrinsic calcium activity in granule cell precursors during the switch from tangential to radial migration. Neuronal activity is found to be necessary for the positioning and survival of granule cell precursors in the olfactory bulb layers.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Immunology
Ayla Batu Ozturk, Nail Can Ozturk, Furkan Ayaz
Summary: Many neurodegenerative diseases show neuroinflammation and impaired neuron production in the hippocampus. Immunotherapeutic strategies targeting microglia may be problematic. Instructing monocytes/macrophages from the periphery could be a less invasive strategy. However, the interaction between CNS neurons and macrophages is poorly understood.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yumi Tsuneura, Masahito Sawahata, Norimichi Itoh, Ryoya Miyajima, Daisuke Mori, Takao Kohno, Mitsuharu Hattori, Akira Sobue, Taku Nagai, Hiroyuki Mizoguchi, Toshitaka Nabeshima, Norio Ozaki, Kiyofumi Yamada
Summary: Reelin, a crucial extracellular matrix protein secreted by Cajal-Retzius cells, plays important roles in brain development and neuronal functions. Reductions in Reelin are associated with brain dysfunctions in mental disorders like schizophrenia. A recent study identified a novel deletion in RELN encoding Reelin in Japanese schizophrenia patients, leading to abnormalities in brain structures and social behavior.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Article
Neurosciences
Takao Honda, Yuki Hirota, Kazunori Nakajima
Summary: Loss-of-function mutations in Reelin and DAB1 signaling pathways disrupt proper neuronal positioning in the cerebral neocortex and hippocampus, and this study reveals that the Dab1 gene dosage has unique dependencies on neuronal migration and positioning in different brain regions.
Article
Clinical Neurology
Wentong Hong, Pifang Gong, Xinjie Pan, Yitong Liu, Guibo Qi, Congcong Qi, Song Qin
Summary: Kruppel-like Factor 7 (KLF7), a zinc finger transcription factor, plays a critical role in cellular differentiation, tumorigenesis, and regeneration. Mutations in Klf7 are associated with autism spectrum disorder characterized by neurodevelopmental delay and intellectual disability. Our study reveals that KLF7 regulates neurogenesis and neuronal migration during mouse cortical development. Depletion of KLF7 in neural progenitor cells leads to agenesis of the corpus callosum, defects in neurogenesis, and impaired neuronal migration in the neocortex. Transcriptomic profiling analysis identifies p21 and Rac3 as KLF7-regulated genes involved in neuronal differentiation and migration. These findings contribute to our understanding of the potential mechanisms underlying neurological defects associated with Klf7 mutations.
Article
Biology
Jose M. Serrano-Morales, Maria D. Vazquez-Carretero, Pablo Garcia-Miranda, Ana E. Carvajal, Maria L. Calonge, Anunciacion A. Ilundain, Maria J. Peral
Summary: Colon cancer is a complex disease with various genetic, environmental, and lifestyle risk factors. This study investigated the role of the protein reelin in the initiation and progression of colon cancer using both mouse models and human samples. The results suggest that reelin may serve as a potential biomarker for predicting the progression of colon pathology, and its dysregulation may contribute to the development of colon cancer. These findings provide valuable insights into the molecular mechanisms of colon cancer and could have implications for its diagnosis and treatment.
Article
Neurosciences
Catherine R. Wasser, Gordon C. Werthmann, Eric M. Hall, Kristina Kuhbandner, Connie H. Wong, Murat S. Durakoglugil, Joachim Herz
Summary: This study demonstrates the role of alternative splicing and release of Apoer2-ICD in regulating translating transcripts in the mouse hippocampus. Dysregulated Apoer2 splicing may contribute to synaptic deficits and neurodegeneration in Alzheimer's disease. These findings suggest the Reelin/Apoer2 pathway as a potential target for AD therapeutics.
MOLECULAR NEURODEGENERATION
(2023)
Article
Neurosciences
Orly Reiner, Arpan Parichha, Tamar Sapir
Summary: Advancements in understanding human neuronal migration disorders using mouse models have been significant, despite the notable differences between human and mouse genetic information and developmental processes. The development of human brain organoid models has sparked excitement in modeling human neuronal migration diseases. Differences in gene expression, morphology, and migratory routes between human and mouse brains highlight the need for further study.
CURRENT OPINION IN NEUROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Zane R. Lybrand, Sonal Goswami, Jingfei Zhu, Veronica Jarzabek, Nikolas Merlock, Mahafuza Aktar, Courtney Smith, Ling Zhang, Parul Varma, Kyung-Ok Cho, Shaoyu Ge, Jenny Hsieh
Summary: In this study, researchers identified a critical window of activity associated with the aberrant maturation of adult-born granule cells (abGCs) in the mammalian hippocampus, which contributes to epileptogenesis. Silencing aberrant abGCs during this critical period reduced abnormal dendrite morphology, cell migration, and seizures in a mouse model of temporal lobe epilepsy. Furthermore, the study demonstrated that GABA-mediated amplification of intracellular calcium regulates the early critical period of activity.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Mohammad I. K. Hamad, Abdalrahim Jbara, Obada Rabaya, Petya Petrova, Solieman Daoud, Nesrine Melliti, Maurice Meseke, David Lutz, Elisabeth Petrasch-Parwez, Jan Claudius Schwitalla, Melanie D. Mark, Stefan Herlitze, Gebhard Reiss, Joachim Herz, Eckart Foerster
Summary: Reelin plays a crucial role in controlling early network activity by modulating GABA(B)R function, affecting the excitability of the cortical network.
JOURNAL OF NEUROCHEMISTRY
(2021)
Review
Neurosciences
Janne Hakanen, Nicolas Parmentier, Leonie Sommacal, Dario Garcia-Sanchez, Mohamed Aittaleb, Didier Vertommen, Libing Zhou, Nuria Ruiz-Reig, Fadel Tissir
Summary: The planar cell polarity protein Celsr3 and the microtubule depolymerizing protein Kif2a cooperatively specify the directionality of neuroblasts tangential migration in the postnatal brain, providing new insights into the mechanisms of neuroblast migration.
PROGRESS IN NEUROBIOLOGY
(2022)
Article
Biology
Alessia Caramello, Christophe Galichet, Karine Rizzoti, Robin Lovell-Badge
Summary: During embryonic development, timely regulation of the switch between radial glial cells, neurons, and astrocytes is crucial for coordinated interactions in the brain. The deletion of the SOX9 gene in early mouse brain development resulted in compromised dentate gyrus development, highlighting the importance of SOX9 in regulating astroglial potential acquisition in the cortical hem. This study demonstrates the formation of a local network between astrocytic and neuronal progenitors from adjacent domains, essential for brain morphogenesis.
Article
Oncology
Yasuyuki Mizutani, Hiroki Kobayashi, Tadashi Iida, Naoya Asai, Atsushi Masamune, Akitoshi Hara, Nobutoshi Esaki, Kaori Ushida, Shinji Mii, Yukihiro Shiraki, Kenju Ando, Liang Weng, Seiichiro Ishihara, Suzanne M. Ponik, Matthew W. Conklin, Hisashi Haga, Arata Nagasaka, Takaki Miyata, Makoto Matsuyama, Tomoe Kobayashi, Tsutomu Fujii, Suguru Yamada, Junpei Yamaguchi, Tongtong Wang, Susan L. Woods, Daniel Worthley, Teppei Shimamura, Mitsuhiro Fujishiro, Yoshiki Hirooka, Atsushi Enomoto, Masahide Takahashi
Article
Cardiac & Cardiovascular Systems
Akitoshi Hara, Hiroki Kobayashi, Naoya Asai, Shigeyoshi Saito, Takahiro Higuchi, Katsuhiro Kato, Takahiro Okumura, Yasuko K. Bando, Mikito Takefuji, Yasuyuki Mizutani, Yuki Miyai, Shoji Saito, Shoichi Maruyama, Keiko Maeda, Noriyuki Ouchi, Arata Nagasaka, Takaki Miyata, Shinji Mii, Noriyuki Kioka, Daniel L. Worthley, Toyoaki Murohara, Masahide Takahashi, Atsushi Enomoto
CIRCULATION RESEARCH
(2019)
Article
Cell Biology
Kanako Saito, Mayumi Okamoto, Yuto Watanabe, Namiko Noguchi, Arata Nagasaka, Yuta Nishina, Tomoyasu Shinoda, Akira Sakakibara, Takaki Miyata
Article
Cell Biology
Ryotaro Kawasoe, Tomoyasu Shinoda, Yuki Hattori, Mami Nakagawa, Trung Quang Pham, Yoshihiro Tanaka, Ken Sagou, Kanako Saito, Satoru Katsuki, Tomomi Kotani, Akihito Sano, Toshihiko Fujimori, Takaki Miyata
DEVELOPMENT GROWTH & DIFFERENTIATION
(2020)
Article
Multidisciplinary Sciences
Yuki Hattori, Yu Naito, Yoji Tsugawa, Shigenori Nonaka, Hiroaki Wake, Takashi Nagasawa, Ayano Kawaguchi, Takaki Miyata
NATURE COMMUNICATIONS
(2020)
Article
Neurosciences
Chenmin Li, Hiroyuki Konishi, Kimitoshi Nishiwaki, Katsuaki Sato, Takaki Miyata, Hiroshi Kiyama
Summary: Embryonic microglia were effectively depleted for several days throughout the CNS using a specific ablation system, showing its potential for studying the embryonic functions of microglia. This system was specific for microglia and did not affect CNS-associated macrophages, allowing for targeted research on the roles of microglia in CNS development.
NEUROSCIENCE RESEARCH
(2021)
Article
Cell Biology
Arata Nagasaka, Takaki Miyata
Summary: The study found that the apical surfaces of different regions of the embryonic brain wall in mice have distinct mechanical properties, with the pallium region having higher stiffness than the ganglionic eminence, possibly due to differential densification of NPC apices. The greater pre-stress in the ganglionic eminence may indicate how the initially apically concave wall transforms into an apically convex eminence.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Anatomy & Morphology
Koichiro Tsujikawa, Kanako Saito, Arata Nagasaka, Takaki Miyata
Summary: The mechanical interaction between developing brains and embryonic scalp layers is still unknown. The research found that in embryonic mice before ossification, a stretcher-compressor relationship develops between the brain and the scalp, underlying their mechanically interdependent development.
DEVELOPMENTAL DYNAMICS
(2022)
Article
Neurosciences
Yuki Hattori, Haruka Itoh, Yoji Tsugawa, Yusuke Nishida, Kaori Kurata, Akiyoshi Uemura, Takaki Miyata
Summary: This study reveals the important role of pericytes in the distribution and function of microglia in the developing brain. Pericytes promote microglial proliferation and the production of soluble factors, indirectly affecting microglial effects on neural progenitors.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Koyo Tsujikawa, Kohei Hamanaka, Yuichi Riku, Yuki Hattori, Norikazu Hara, Yohei Iguchi, Shinsuke Ishigaki, Atsushi Hashizume, Satoko Miyatake, Satomi Mitsuhashi, Yu Miyazaki, Mayumi Kataoka, Li Jiayi, Keizo Yasui, Satoshi Kuru, Haruki Koike, Kenta Kobayashi, Naruhiko Sahara, Norio Ozaki, Mari Yoshida, Akiyoshi Kakita, Yuko Saito, Yasushi Iwasaki, Akinori Miyashita, Takeshi Iwatsubo, Takeshi Ikeuchi, Takaki Miyata, Gen Sobue, Naomichi Matsumoto, Kentaro Sahashi, Masahisa Katsuno
Summary: This study identified the role of Filamin-A in promoting tau aggregation in progressive supranuclear palsy (PSP) patients without tau mutations. It found that nonmutated tau interacts with actin filaments through increased levels of Filamin-A, resulting in enhanced phosphorylation and insolubility of tau. The study also showed that reducing Filamin-A levels corrected aberrant tau levels in PSP cell cultures.
Article
Neurosciences
Shengming Wang, Yu Fu, Takaki Miyata, Sakiko Matsumoto, Tomoyasu Shinoda, Kyoko Itoh, Akihiro Harada, Shinji Hirotsune, Mingyue Jin
Summary: This study reveals the functional cooperation between aSyn and tau during brain development. Deletion of aSyn and tau alters the balance between progenitor cell proliferation and neurogenesis, resulting in an overproduction of early born neurons. Furthermore, there is a reduction in neural progenitor cells in the aSyn-/-tau-/- cortex, leading to diminished gliogenesis. Additionally, expansion and maturation of macroglial cells are suppressed in the aSyn-/-tau-/- postnatal brain, resulting in reduced brain size and cortical thickness.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Cell Biology
Yosuke Ogura, Kentaro Sahashi, Tomoki Hirunagi, Madoka Iida, Takaki Miyata, Masahisa Katsuno
Summary: Spinal and bulbar muscular atrophy (SBMA) is an adult-onset neurodegenerative disease caused by the expansions of CAG repeats in the androgen receptor (AR) gene. This study found that upregulation of Mid1 gene expression in motor neurons contributes to vulnerability and axonogenesis defects in SBMA.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Hiroki Katsuta, Satoru Okuda, Kazuaki Nagayama, Hiroaki Machiyama, Satoru Kidoaki, Masashi Kato, Masahiro Sokabe, Takaki Miyata, Hiroaki Hirata
Summary: In this study, the researchers discovered that contractile force generated in actomyosin stress fibers is transmitted to the extracellular matrix. They found that efficient force transmission relies on actin crosslinking by alpha-actinin. Decreasing the density of actin crosslinks led to decreased traction force exertion and a decrease in the difference in cell migration speed dependent on ECM rigidity. These findings shed light on the importance of alpha-actinin and actin crosslinking in cell mechanosensing and response to ECM rigidity.
Article
Multidisciplinary Sciences
Daisuke Saito, Ryosuke Tadokoro, Arata Nagasaka, Daisuke Yoshino, Takayuki Teramoto, Kanta Mizumoto, Kenichi Funamoto, Hinako Kidokoro, Takaki Miyata, Koji Tamura, Yoshiko Takahashi
Summary: Unlike mammals, avian early embryos have PGCs that utilize blood circulation to migrate to the somatic gonadal primordium. Our research shows that PGCs are arrested at a specific site in the capillary plexus, enabled by increased stiffness mediated by actin polymerization. They then soften to squeeze through the endothelial lining.
Article
Cell Biology
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
Summary: By tracking cells, researchers found that CD206+ macrophages frequently enter the inner surface of the mouse cerebral wall and convert into microglia at embryonic day 12. It was also discovered that intraventricular macrophages are supplied transepithelially from the roof plate. This study demonstrates that the roof plate->ventricle->pallium route is essential for microglial colonization into the embryonic mouse brain.