| Budget Amount *help |
¥29,100,000 (Direct Cost: ¥29,100,000)
Fiscal Year 2002: ¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 2001: ¥17,100,000 (Direct Cost: ¥17,100,000)
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| Research Abstract |
SUMMARY OF Our research goal was
Our research goal was to understand the molecular basis of functional development of somatosensory cortex. We made three approaches to address this research goal. First, the development of cortical area proceeds through several steps. In the early forebrain, morphogens, like FGF8, Wnt, and Shh are expressed in a gradient according to body axes and induce a series of transcription factors which in turn define the area specific properties of forebrain. One of the area specific genes is cadherin6, which is expressed in the region giving rise to future somatosensory cortex. The function of cadherin6 was uncertain in early areazation. Thus, we studied the function by using whole embryo culture system and electroporation of cadherin6 or a dominant negative form of the molecule. We found that cadherin6 is essential for stabilization of the future somatosensory area in the early forebrain. This study is further developed as a high-through put analysis of genes e
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xpressed in early somatosensory area by DNA microarry as well as identification of enhancers for area specific expression of cadherin6 genes using a BAC system. Second, genetically established cortical areas are further differentiated by innervations from subcortical area, that is, thalamic nuclei. We studied the central pattern formation mechanism. Several knockout mouse lines suggest the existence of genes for pattern formation of somatosensory cortex. In this area, the representation of peripheral whisker patterns are topographically arranged and called as barrel map. We asked the role of
peripheral pattern on the central pattern formation by using an Adenovirus vector harboring chick Shh cDNA which is essential for whisker development. The virus was infected in utero to embryo epidermis, leading to abnormal whisker pattern. The central pattern was the topographic map of the peripheral map. This result showed that the peripheral pattern is the final determinant of the central pattern. Third, the innervated thalamic terminals make excitatory synapses with cortical layer 4 neurons. The early synapses just after birth contains only NMDA receptors, thus are functionally silent. During critical period (6-7days after birth), silent synapses are converted to active synapses containing AMPA receptors too. We found that brain-derived neurotrophic factor, BDNF is essential for this activation process synergistically with neuronal activity mediated by NMDA receptor. This study is further developing as a trafficking mechanism study of AMAP receptors. Less
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