Leamey Catherine A, Glendining Kelly A, Kreiman Gabriel, Kang Ning-Dong, Wang Kuan H, Fassler Reinhard, Sawatari Atomu, Tonegawa Susumu, Sur Mriganka
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cereb Cortex. 2008 Jan;18(1):53-66. doi: 10.1093/cercor/bhm031. Epub 2007 May 2.
Adult neocortical areas are characterized by marked differences in cytoarchitecture and connectivity that underlie their functional roles. The molecular determinants of these differences are largely unknown. We performed a microarray analysis to identify molecules that define the somatosensory and visual areas during the time when afferent and efferent projections are forming. We identified 122 molecules that are differentially expressed between the regions and confirmed by quantitative polymerase chain reaction 95% of the 20 genes tested. Two genes were chosen for further investigation: Bcl6 and Ten_m3. Bcl6 was highly expressed in the superficial cortical plate corresponding to developing layer IV of somatosensory cortex at postnatal day (P) 0. This had diminished by P3, but strong expression was found in layer V pyramidal cells by P7 and was maintained until adulthood. Retrograde tracing showed that Bcl6 is expressed in corticospinal neurons. Ten_m3 was expressed in a graded pattern within layer V of caudal cortex that corresponds well with visual cortex. Retrograde tracing and immunostaining showed that Ten_m3 is highly expressed along axonal tracts of projection neurons of the developing visual pathway. Overexpression demonstrated that Ten_m3 promotes homophilic adhesion and neurite outgrowth in vivo. This suggests an important role for Ten_m3 in the development of the visual pathway.
成年新皮质区域的特点是细胞结构和连接性存在显著差异,这些差异构成了它们的功能基础。这些差异的分子决定因素在很大程度上尚不清楚。我们进行了微阵列分析,以确定在传入和传出投射形成期间定义体感区和视觉区的分子。我们鉴定出122种在区域间差异表达的分子,并通过定量聚合酶链反应对20个测试基因中的95%进行了验证。选择了两个基因进行进一步研究:Bcl6和Ten_m3。Bcl6在出生后第0天(P0)对应于体感皮层发育中的第IV层的浅层皮质板中高度表达。到P3时这种表达减弱,但在P7时在第V层锥体细胞中发现强表达,并一直维持到成年。逆行追踪显示Bcl6在皮质脊髓神经元中表达。Ten_m3在尾侧皮质第V层以梯度模式表达,与视觉皮层非常吻合。逆行追踪和免疫染色显示Ten_m3在发育中的视觉通路投射神经元的轴突束中高度表达。过表达表明Ten_m3在体内促进同嗜性黏附和神经突生长。这表明Ten_m3在视觉通路发育中起重要作用。