| Budget Amount *help |
¥16,500,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2007: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2006: ¥8,700,000 (Direct Cost: ¥8,700,000)
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| Research Abstract |
In the central nervous system (CNS) of vertebrates, the retina is an accessible model system to study various issues in the neuroscience field and medical science. The retina is relatively simple, thin layer structure of neural tissue that is located posterior part of the eye. Many things have been learned about the anatomy, physiology, cell metabolism and development of the retina. However, the retina still must solve several important scientific and medical problems. We have been studying to understand the molecular mechanisms of vertebrate retinal development from several aspects, including early eye formation, cell fate determination of photoreceptors, and network formation of the retina.
The establishment of precise synaptic connections between neurons in the developing and mature CNS is crucial for normal nervous system functions, including perception, memory and cognition. Thus, elucidating the mechanisms by which synapses develop and are modified is a central question in neurobi
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ology. Over the past few decades, a large number of protein components that are required for synapse morphogenesis and neurotransmitter release have been -identified. However, the molecules and mechanisms underlying specific synapse connections in the vertebrate CNS are still poorly understood.
In this study we identify pikachurin, a novel dystroglycan ligand, and observe its localization to the synaptic cleft in the photoreceptor ribbon synapse. Pikachurin null mice display improper apposition of the bipolar terminus to the ribbon synapse, resulting in alterations in synaptic signal transmission and visual function. We observed co-localization of pikachurin with DGC molecules and direct binding of pikachurin with a-dystroglycan, an extracellular component of DGC. Our results suggest that pikachurin is the first dystroglycan ligand to interact with the presynaptic DGC, and demonstrate its essential role in precise synapse formation. This may also advance our understanding of the molecular mechanisms underlying the retinal electrophysiological abnormalities observed in muscular dystrophy patients. Less
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