Brain-derived neurotrophic factor participates in determination of neuronal laminar fate in the developing mouse cerebral cortex
Brain-derived neurotrophic factor participates in determination of neuronal laminar fate in the developing mouse cerebral cortex
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DOI：
10.1523/jneurosci.4251-06.2006
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发表时间：
2006-12-20
影响因子：
5.3
通讯作者：
Furukawa, Shoei
中科院分区：
文献类型：
--
作者：
Fukumitsu, Hidefumi;Ohtsuka, Masanari;Furukawa, Shoei
发育中的大脑皮层中板层的形成需要精确调控的皮层祖细胞的产生和迁移。为了检测脑源性神经营养因子（BDNF）可能参与皮质层的形成，我们研究了BDNF蛋白和抗BDNF抗体分别注入13.5天龄小鼠胚胎的端脑室空间的影响。BDNF改变了原本预定用于第IV层的神经元的位置、基因表达特性和投射，使其变为用于大脑皮层的更深层（V和VI）的神经元的位置、基因表达特性和投射，而抗BDNF抗体改变了上层II/III的神经元的一些位置、基因表达特性和投射。进一步的分析表明，BDNF只有在其亲本祖细胞在大约S期暴露于BDNF时才改变神经元的层状命运，并且通过加速S期的完成、下调Pax 6表达、以及抑制神经元的增殖，来加速子代神经元从心室增殖池中退出的时间。（配对盒基因6）表达，一种用于产生上层神经元的必需转录因子，以及皮质祖细胞在脑室区中的核间迁移。这些观察结果表明，BDNF参与形成发育中的大脑皮层神经元层的过程。因此，BDNF可以算作是一个关键的外在因素，调节皮层神经元的层状命运。
Lamina formation in the developing cerebral cortex requires precisely regulated generation and migration of the cortical progenitor cells. To test the possible involvement of brain- derived neurotrophic factor ( BDNF) in the formation of the cortical lamina, we investigated the effects of BDNF protein and anti- BDNF antibody separately administered into the telencephalic ventricular space of 13.5-d- old mouse embryos. BDNF altered the position, gene- expression properties, and projections of neurons otherwise destined for layer IV to those of neurons for the deeper layers, V and VI, of the cerebral cortex, whereas anti- BDNF antibody changed some of those of neurons of upper layers II/III. Additional analysis revealed that BDNF altered the laminar fate of neurons only if their parent progenitor cells were exposed to it at approximately S- phase and that it hastened the timing of the withdrawal of their daughter neurons from the ventricular proliferating pool by accelerating the completion of S- phase, downregulation of the Pax6 ( paired box gene 6) expression, an essential transcription factor for generation of the upper layer neurons, and interkinetic nuclear migration of cortical progenitors in the ventricular zone. These observations suggest that BDNF participates in the processes forming the neuronal laminas in the developing cerebral cortex. BDNF can therefore be counted as one of the key extrinsic factors that regulate the laminar fate of cortical neurons.