BDNF-modulated spatial organization of Cajal-Retzius and GABAergic neurons in the marginal zone plays a role in the development of cortical organization
BDNF-modulated spatial organization of Cajal-Retzius and GABAergic neurons in the marginal zone plays a role in the development of cortical organization
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DOI：
10.1093/cercor/bhi128
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发表时间：
2006-04-01
期刊：
影响因子：
3.7
通讯作者：
Soriano, E
中科院分区：
文献类型：
--
作者：
Alcántara, S;Pozas, E;Soriano, E
本研究利用巢蛋白-BDNF转基因小鼠，为早期脑源性神经营养因子（BDNF）信号传导增加提供了模型，以研究BDNF在皮质结构发育中的作用。我们的研究结果表明，BDNF的过早和均匀表达，虽然保留了从神经节突起到皮层的切向迁移，但损害了gaba能神经元最终的径向迁移，以及它们在适当皮层的整合。此外，Cajal-Retzius （CR）细胞和gaba能神经元响应BDNF信号在皮质边缘区（MZ）分离，导致交替模式和柱状皮质组织，其中不同神经元群的迁移受到特异性影响。这些结果表明，CR和gaba能神经元都在指导后期生成的皮层神经元的径向迁移中发挥作用，并且这些细胞在MZ中的空间分布对正确皮层组织的发育至关重要。此外，MZ中CR细胞分泌的reelin不足以指导晚生神经元向皮层上层迁移，这很可能需要在V-VI层中存在分泌reelin的中间神经元。我们认为除了调节reelin的表达外，BDNF还调节MZ中CR和gaba能神经元的斑块分布，并且这种空间分布参与了解剖和/或功能柱和卷曲结构的形成。
The present study utilizes nestin-BDNF transgenic mice, which offer a model for early increased brain-derived neurotrophic factor (BDNF) signalling, to examine the role of BDNF in the development of cortical architecture. Our results demonstrate that the premature and homogeneous expression of BDNF, while preserving tangential migration from the ganglionic eminence to the cortex, impairs the final radial migration of GABAergic neurons, as well as their integration in the appropriate cortical layers. Moreover, Cajal-Retzius (CR) cells and GABAergic neurons segregate in the cortical marginal zone (MZ) in response to BDNF signalling, leading to an alternating pattern and a columnar cortical organization, within which the migration of different neuronal populations is specifically affected. These results suggest that both CR and GABAergic neurons play a role in directing the radial migration of late-generated cortical neurons, and that the spatial distribution of these cells in the MZ is critical for the development of correct cortical organization. In addition, reelin secreted by CR cells in the MZ is not sufficient to direct the migration of late-born neurons to the upper cortical layers, which most likely requires the presence of reelin-secreting interneurons in layers V-VI. We propose that in addition to modulating reelin expression, BDNF regulates the patched distribution of CR and GABAergic neurons in the MZ, and that this spatial distribution is involved in the formation of anatomical and/or functional columns and convoluted structures.