Molecular mechanism of brain development
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Our research goal is to understand the molecular
mechanisms of neuronal@differentiation, brain wiring and functional development
of our brain. For this@purpose, we analyze the functions of the genes which are
involved in the brain development using mice and zebrafish as model animals. We
use the results from these studies to develop the novel therapeutic approaches
of neuronal regeneration. We further study the molecular mechanisms of higher
brain functions such as learning, memory and emotion. These studies will help us
to understand the molecular and cellular mechanisms of neuropsychiatric
disorders and contribute to develop the novel therapeutic methods of these human
disorders. |
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Analysis for the mechanism of the determination of neuronal positioning and neurite extension
in the developing CNS |
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To make proper neural circuit, it is
important that newly generated neurons migrate into their collect destination
and make synapses with their counterparts. Cyclin-dependent kinase 5 (Cdk5) is
involved in multiple important processes including neuronal migration and
positioning, neurite extension and axon guidance in developing CNS. We aim to reveal
the molecular mechanisms of these processes through the analysis of
Cdk5/p35-deficient mice. We also focus on collapsing response mediator protein
2 (CRMP2) which we identified as one of Cdk5 substrate. We analyze the role of
CRMP family proteins and phospho-dependent modification of CRMP function using
mutant mice. In addition, we use zebrafish Rohon-Beard (RB) primary sensory
neurons as a model system, and are analyzing the role of CRMP family in the
determination of cellular position and in the axonal outgrowth of RB neurons in
the developing zebrafish embryos.
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Analysis for the mechanism of higher brain function using genetically modified
mice |
Cdk5/p35 phosphorylates multiple proteins
which present in pre- andpost-synapse and are involved in synaptic plasticity.
Through the analyses of p35-deficient mice and Cdk5 conditional KO mice,
importance of Cdk5/p35 has been emphasized in higher brain functions such as
learing and memory and emotion. We continue the investigation of mechanism of
higher brain functions with particular interest on phosphorylation signaling
through the analysis of mutant mice.
Research toward understanding of etiology and pathophysiology, and developing
therapeutic
approach of human psycho-neurological disorders |
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In mammalian, newly generated neurons in
the adult brain plays an important role for learning and memory. In addition,
in the medical aspect, regulation of the proliferation and differentiation of
the neural stem cells (NSCs) is one of the key technique for regenerative
medicine of central nervous system (CNS). NSCs transplantation strategies might
have therapeutic promise in treating adult CNS disorders characterized by loss
of neuronal or glial cells. In the adult teleost brain, NSCs are distributed in
various brain regions, and continue to produce new neurons and glial cells
through their life. We focus on the molecular mechanisms of proliferation and
differentiation of NSCs in the adult zebrafish optic tectum, and try to reveal
the general molecular machinery of proliferation and differentiation of NSCs.
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Analysis for proliferation and differentiation of the neural stem cells in the adult zebrafish
opitc tectum |
Although some of responsible genes in
familial cases have been identified in neurodegenerative disorders, most of
their etiologies and pathophysiologies remain elucidated. We found
neurodegeneration and neuronal loss in some types of Cdk5 conditional KO mice.
Using these mutant mice, we approach to pathophysiologies of neurodegenerative
disorders. In addition, we use mouse models of Alzheimer disease and Parkinson
disease for our research.
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