Ohshima Lab                                             本文へジャンプ
Molecular mechanism of brain development

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.

Analysis for the mechanism of the determination of neuronal positioning and neurite extension in the developing CNS
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.

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.

Analysis for the mechanism of adult neurogenesis in the zebrafish brain
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 other 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.

Research toward understanding of etiology and pathophysiology and developing therapeutic approach of human psycho-neurological disorders

Although causative genes of some familial neurodegenerative disorders were identified, etiology and pathophysiology of those disorders remain unelucidated. In our laboratory, we try to understand the pathophysiology of neurodegenerative disorders by using Cdk5-deficient model mice. We will also utilize mouse models of Alzheimer’s disease and Parkinson’s disease for this purpose.