A5025974163- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Hedgehog Signaling Pathway Studies
- Developmental Biology and Gene Regulation
- Axon Guidance and Neuronal Signaling
- Receptor Mechanisms and Signaling
- Neurobiology and Insect Physiology Research
- Genetics and Neurodevelopmental Disorders
- Cellular transport and secretion
- bioluminescence and chemiluminescence research
- Virus-based gene therapy research
- Photochromic and Fluorescence Chemistry
- Cholinesterase and Neurodegenerative Diseases
- Anesthesia and Neurotoxicity Research
- Hereditary Neurological Disorders
- Medicinal Plants and Neuroprotection
- interferon and immune responses
- Galectins and Cancer Biology
- Wnt/β-catenin signaling in development and cancer
- Ocular Oncology and Treatments
- Congenital limb and hand anomalies
- Angiogenesis and VEGF in Cancer
- Neurological disorders and treatments
- Congenital heart defects research
- Pancreatic function and diabetes
Kyoto University
1990-2023
Saiseikai Nakatsu Hospital
2019
Osaka University
2007-2016
Mitsubishi Chemical (Japan)
2004
Mitsubishi Group (Japan)
2003-2004
Japan Science and Technology Agency
2004
Howard Hughes Medical Institute
1994-2003
Columbia University
1994-2003
Johns Hopkins University
1995
The differentiation of floor plate cells and motor neurons can be induced by Sonic hedgehog (SHH), a secreted signaling protein that undergoes autoproteolytic cleavage to generate amino- carboxy-terminal products. We have found both are the amino-terminal product SHH (SHH-N). threshold concentration SHH-N required for neuron induction is about 5-fold lower than induction. Higher concentrations induce at expense differentiation. Our results suggest notochord in vivo mediated exposure neural...
The metabotropic glutamate receptors are coupled to intracellular signal transduction via G-proteins and consist of a family at least five different subtypes, termed mGluR1-mGluR5. We studied the mechanism pharmacological characteristics rat mGluR3 mGluR4 subtypes in Chinese hamster ovary cells permanently expressing cloned receptors. Both inhibit forskolin-stimulated accumulation cAMP formation response agonist interaction. Consistent with high degree sequence similarity mGluR2, closely...
Sonic hedgehog signaling controls the differentiation of motor neurons in ventral neural tube, but intervening steps are poorly understood. A differential screen a cDNA library derived from single Shh-induced neuron has identified novel homeobox gene MNR2, expressed by progenitors and transiently postmitotic neurons. The ectopic expression MNR2 cells initiates program somatic characterized homeodomain proteins, neurotransmitter phenotype, axonal trajectory. Our results suggest that...
An early and fundamental step of the laminar organization developing neocortex is controlled by developmental programs that critically depend on activities reelin-positive cells in marginal zone. However, ontogeny remained elusive. To gain insights into spatial temporal regulation zone cell development, we used a transgenic mouse line which defined green fluorescent protein (GFP) transgene as novel reliable molecular marker from stages their development. We further exo utero...
1. 2-(Carboxycyclopropyl)glycines (CCGs) are conformationally restricted glutamate analogues and consist of eight isomers including L- D-forms. The agonist potencies selectivities these compounds for metabotropic receptors (mGluRs) were studied by examining their effects on the signal transduction representative mGluR1, mGluR2 mGluR4 subtypes in Chinese hamster ovary cells expressing individual cloned receptors. 2. Two extended L-CCG, L-CCG-I L-CCG-II, effectively stimulated...
Metabotropic glutamate receptors consist of at least six different subtypes termed mGluR1-mGluR6. They belong to the family G protein-coupled and commonly possess an unusually large extracellular domain preceding seven transmembrane segments. mGluR1 mGluR2 show similar affinities for L-glutamate but distinct patterns in their responsiveness quisqualate trans-1-amino-1,3-cyclopentane-dicarboxylate (tACPD). To assign structural determinants agonist selectivities, we constructed a series...
In the developing spinal cord, motor neurons acquire columnar subtype identities that can be recognized by distinct profiles of homeodomain transcription factor expression. The mechanisms direct differentiation neuron from an apparently uniform group progenitors remain poorly defined. chick embryo,the Mnx class protein MNR2 is expressed selectively progenitors, and has been implicated in specification fate. We show here expression persists postmitotic populate median column (MMC), whereas...
Tlx belongs to a class of orphan nuclear receptors that underlies many aspects neural development in the CNS. However, fundamental roles played by control eye developmental programs remain elusive. By using knock-out (KO) mice, we show here is expressed retinal progenitor cells neuroblastic layer during period formation, and it critical for controlling generation appropriate numbers progenies through activities cell cycle-related molecules, cyclin D1 p27 Kip1 . expression restricted Müller...
Laminar organization, a fundamental neural architecture in the CNS, is prominent feature of neocortex, where cortical neurons spatially distinct layers are generated from common progenitors temporally manner during development. Despite many advances characterization molecular mechanisms radial migration neurons, way which early-late temporal sequence neuron generation linked with deep-superficial spatial cell body positioning remains obscure. Using vivo electroporation-mediated gene...
Cajal-Retzius (CR) cells are early-generated transient neurons and important in the regulation of cortical neuronal migration laminar formation. Molecular entities characterizing CR cell identity, however, remain largely elusive. We purified mouse expressing GFP to homogeneity by fluorescence-activated sorting examined a genomewide expression profile at embryonic postnatal periods. identified 49 genes that exceeded hybridization signals >10-fold compared with non-CR day 13.5, 2, or both....
Abstract Background Robo1, Robo2 and Rig-1 (Robo3), members of the Robo protein family, are candidate receptors for chemorepellents Slit known to play a crucial role in commissural axon guidance spinal cord. However, their roles at other axial levels remain unknown. Here we examine expression proteins by cerebellofugal (CF) axons rostral hindbrain investigate CF pathfinding analysing knockout mice. Results We analysed originating from deep cerebellar neurons rodent embryos, focusing on...
The striatum, the largest nucleus of basal ganglia controlling motor and cognitive functions, can be characterized by a labyrinthine mosaic organization striosome/matrix compartments. It is unclear how formation spatially temporally controlled at cellular level during striatal development. Here, combining in vivo electroporation brain slice cultures, we set up prospective experimental system which differentially labeled striosome matrix cells from time birth followed their distributions...
The domestic chicken is an attractive model system to explore the development and function of brain circuits. Electroporation-mediated retrovirus (including lentivirus) vector-mediated gene transfer techniques have been widely used introduce genetic material into cells. However, it still challenging efficiently transduce postmitotic neurons without harming To overcome this problem, we searched for a virus vector suitable neurons, report here novel recombinant derived from avian...
Hippocampal hyperexcitability is a promising therapeutic target to prevent Aβ deposition in AD since enhanced neuronal activity promotes presynaptic production and release. This article highlights the potential application of perampanel (PER), an AMPA receptor (AMPAR) antagonist approved for partial seizures, as agent AD. Using transgenic mice combined with vivo brain microdialysis primary neurons under oligomeric Aβ-evoked hyperexcitability, acute effects PER on metabolism were...
症例は21歳右利き女性.てんかん家族歴はない.14歳頃から全身けいれん発作を月1回の頻度で認めていた.クロナゼパム,レベチラセタムの加療では改善しなかった.病歴再聴取にて急な動きに誘発される不随意運動が明らかとなり,発作性運動誘発性舞踏アテトーゼ(paroxysmal kinesigenic choreoathetosis; PKC)の責任遺伝子(proline-rich transmembrane protein 2; PRRT2)に変異を認めた.カルバマゼピン少量投与にてけいれん発作およびPKCは完全に消失した.本例ではPRRT2関連疾患として思春期以降もPKCとけいれん発作が併存したがPKCの症状が病的と自覚されていなかった.PRRT2関連疾患のけいれん発作はカルバマゼピンが著効することがあり詳細な病歴聴取が重要である.
The generation of distinct neural subtypes depends on the activities cell-extrinsic and -intrinsic factors during development vertebrate CNS. Previous studies have provided a molecular basis for how progenitors are patterned generate descendants that spatially temporally regulated by inductive signals secreted polarized sources. However, it still remains unknown located at sources is controlled. Sonic hedgehog (Shh), which expressed ventral midline in forebrain, has been shown to play...