A5082773543- Genetics and Neurodevelopmental Disorders
- Epilepsy research and treatment
- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Microtubule and mitosis dynamics
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Cellular transport and secretion
- Gastric Cancer Management and Outcomes
- Axon Guidance and Neuronal Signaling
- Genetic and Kidney Cyst Diseases
- Pharmacological Effects and Toxicity Studies
- Metabolism and Genetic Disorders
- Regulation of Appetite and Obesity
- Helicobacter pylori-related gastroenterology studies
- Ubiquitin and proteasome pathways
- Diet and metabolism studies
- Muscle Physiology and Disorders
- Sarcoma Diagnosis and Treatment
- Neonatal and fetal brain pathology
- RNA Research and Splicing
- Fetal and Pediatric Neurological Disorders
- Neurological diseases and metabolism
- Metastasis and carcinoma case studies
- Gastrointestinal Tumor Research and Treatment
The University of Tokyo
2007-2025
Hebei Rehabilitation Hospital
2025
Kumamoto University
2024
University of California, San Diego
2000-2022
Teikyo University
2002-2019
Tokyo Medical University
2000-2011
Tokyo Women's Medical University
1998-2001
Institute of Developmental Physiology
2001
National Institute of Dental and Craniofacial Research
2001
Humans with mutations in either DCX or LIS1 display nearly identical neuronal migration defects, known as lissencephaly. To define subcellular mechanisms, we have combined vitro assays retroviral transduction. Overexpression of wild-type Dcx Lis1, but not patient-related mutant versions, increased rates. overexpression rescued the defect Lis1+/− neurons. Lis1 localized predominantly to centrosome, and after disruption microtubules, redistributed perinuclear region. outlined microtubules...
We retrospectively studied patients with myoclonic-astatic epilepsy of early childhood (MAE) to investigate the most effective treatment and long-term seizure intellectual prognosis.Eighty-one MAE were recruited from among 3600 according ILAE criteria MAE.We investigated clinical characteristics ultimate prognosis medical records. The effects various antiepileptic drugs, ketogenic diet ACTH treatments on seizures (MS/AS), apparently a hallmark this unique epileptic syndrome, also...
Increased levels of lactate, an end-product glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These in lactate can result decreased brain pH, which has implicated patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed five mouse models schizophrenia, bipolar disorder, and autism, suggesting shared endophenotype among these disorders rather than mere artifacts due...
Humans with heterozygous inactivating mutations of the Lis1 gene display type I lissencephaly, a severe form cortical dysplasia hypothesized to result from abnormal neuronal migration. Previously we reported construction an allelic series in mice analyze effects graded reduction LIS1 protein on pathogenesis this disorder and demonstrated cell autonomous defect migration (Hirotsune et al., 1998). Here report systematic examination consequences dosage neocortical development using wild-type,...
Dendritic morphogenesis and formation of synapses at appropriate dendritic locations are essential for the establishment proper neuronal connectivity. Recent imaging studies provide evidence stabilization dynamic distal branches dendrites by addition new synapses. However, molecules involved in both growth suppression synapse maturation remain to be identified. Here we report two distinct functions doublecortin-like kinases, chimeric proteins containing a microtubule-binding domain kinase...
Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors hippocampus. In current study, subjected to a battery comprehensive behavioral tests, aiming reveal effects loss CDKL5 whole perspective motor, emotional, social, cognition/memory functions, identify...
Cyclin-dependent kinase 5 (Cdk5) null mice exhibit a unique phenotype characterized by perinatal mortality, disrupted cerebral cortical layering attributable to abnormal neuronal migration, lack of cerebellar foliation, and chromatolytic changes neurons in the brainstem spinal cord. Because Cdk5 is expressed both astrocytes, it has been unclear whether this primarily defects or astrocytes. Herein we report reconstitution expression its effect on phenotype. Unlike mice, reconstituted that...
Muscle satellite cells are indispensable for muscle regeneration, but the functional diversity of their daughter is unknown. Here, we show that many Pax7+MyoD− locate both beneath and outside basal lamina during myofiber maturation. A large majority these not self-renewed cells, have different potentials proliferation differentiation from Pax7+MyoD+ myoblasts (classical cells), specifically marked by expression doublecortin (Dcx) gene. Transplantation lineage-tracing experiments demonstrated...
Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is an X-linked rare neurodevelopmental associated with severe sleep disturbances. However, little known about the mechanisms underlying disturbances in CDD patients. Here, we employed electroencephalogram (EEG) recording to characterize sleep–wake behaviors and EEG activity male CDKL5-deficient mice. We found that young adult middle-aged Cdkl5 knockout (KO) mice recapitulated phenotypes patients CDD, including difficulties...
The doublecortin (Dcx) and doublecortin-like kinase 1 (Dclk) genes are developmentally expressed neuronal microtubule-associated proteins. Humans with DCX mutations show a severe defect in hippocampal development, but targeted deletion mouse shows only pyramidal neuron lamination. There is significant sequence overlap between Dcx Dclk, suggesting functional redundancy. Here we that the two display overlapping expression patterns developing hippocampus. Targeted of Dclk no appreciable...
Increased levels of lactate, an end-product glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These in lactate can result decreased brain pH, which has implicated patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed five mouse models schizophrenia, bipolar disorder, and autism, suggesting shared endophenotype among these disorders rather than mere artifacts due...
Primary cilia are microtubule-based sensory organelles whose dysfunction causes ciliopathies in humans. The formation, function, and maintenance of primary depend crucially on intraflagellar transport (IFT); however, the regulatory mechanisms IFT at ciliary tips poorly understood. Here, we identified that ciliopathy kinase Mak is a tip-localized regulator cooperatively acts with Ick, an regulator. Simultaneous disruption