权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Development of Somatosensory Area

体感区开发

基本信息

批准号：
12210020
负责人：
NAKAMURA Shun
金额：
$ 18.62万
依托单位：
National Center of Neurology and Psychiatry
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

SUMMARY OF Our research goal wasOur 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 … More 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 ofperipheral 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

总结我们的研究目标是了解体感皮质功能发育的分子基础。为了实现这一研究目标，我们采取了三种方法。首先，大脑皮层的发育经历了几个步骤。在早期前脑中，形态原如FGF8、Wnt和Shh根据体轴以梯度方式表达，并诱导一系列转录因子，这些转录因子又定义了前脑的区域特异性属性。其中一个区域特异性基因是钙粘蛋白6，它在形成未来躯体感觉皮质的区域表达。在早期定位中，钙粘蛋白6的功能尚不明确。因此，我们利用整个胚胎培养系统和电穿孔的方法研究了钙粘蛋白6的功能。我们发现钙粘蛋白6对于稳定早期前脑中未来的体感区域是必不可少的。这项研究进一步发展成为e-…基因的高通量分析。通过DNA微阵列和BAC系统鉴定钙粘蛋白6基因区域特异性表达的增强子，在早期体感区域表达更多。其次，通过皮质下区域，即丘脑核的神经支配，进一步区分了遗传上已建立的皮质区域。我们研究了中心花纹的形成机制。几个基因敲除的小鼠品系表明存在躯体感觉皮层模式形成的基因。在这一地区，周围胡须图案的表示是按地形排列的，称为桶状地图。我们利用携带鸡须发育所必需的Shh基因的腺病毒载体，研究了外围模式在中心模式形成中的作用。该病毒在宫内感染胚胎表皮，导致胡须图案异常。中心图案为周边图的地形图。这一结果表明，外围模式是中央模式的最终决定因素。第三，支配丘脑的终末与皮质第四层神经元形成兴奋性突触。出生后的早期突触只含有NMDA受体，因此在功能上是沉默的。在关键期(出生后6-7天)，静止性突触也转化为含有AMPA受体的活性突触。我们发现，脑源性神经营养因子在这一激活过程中与NMDA受体介导的神经元活动协同作用是必不可少的。本研究将进一步发展为AMAP受体转运机制的研究。较少