TrkB receptor controls striatal formation by regulating the number of newborn striatal neurons
TrkB receptor controls striatal formation by regulating the number of newborn striatal neurons
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DOI：
10.1073/pnas.1004744108
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发表时间：
2011-01-25
影响因子：
11.1
通讯作者：
Xu, Baoji
中科院分区：
文献类型：
--
作者：
Baydyuk, Maryna;Russell, Theron;Xu, Baoji
在周围神经系统中，目标组织通过在发育过程中产生有限数量的促进生存的神经营养因子来控制支配神经细胞群的最终大小。然而，在很大程度上仍然不清楚是否同样的原理也适用于调节发育中的大脑中神经元群的大小。本研究表明，TrkB受体介导的神经营养因子信号通过促进发育中的中等棘神经元（MSNs）的存活来控制纹状体大小。使用Dlx5/6-Cre转基因选择性删除纹状体祖细胞中的TrkB受体基因，导致后爪扣表型和50%的msn丢失，但不影响纹状体中间神经元。这种损失主要是由于新生儿msnn在其出生地（外侧神经节隆起）的凋亡增加。在msn中，那些表达多巴胺受体D2 （DRD2）的神经元受到的影响最大，这表明这些神经元的急剧丧失以及DRD2和脑啡肽的特异性下调。突变动物的这种特异性表型可能是由于DRD2 msn中TrkB的优先表达。这些发现表明，神经营养物质可以通过促进新生神经元在迁移到最终目的地之前的存活来控制大脑中神经元种群的大小。
In the peripheral nervous system, target tissues control the final size of innervating neuronal populations by producing limited amounts of survival-promoting neurotrophic factors during development. However, it remains largely unknown if the same principle works to regulate the size of neuronal populations in the developing brain. Here we show that neurotrophin signaling mediated by the TrkB receptor controls striatal size by promoting the survival of developing medium-sized spiny neurons (MSNs). Selective deletion of the gene for the TrkB receptor in striatal progenitors, using the Dlx5/6-Cre transgene, led to a hindpaw-clasping phenotype and a 50% loss of MSNs without affecting striatal interneurons. This loss resulted mainly from increased apoptosis of newborn MSNs within their birthplace, the lateral ganglionic eminence. Among MSNs, those expressing the dopamine receptor D2 (DRD2) were most affected, as indicated by a drastic loss of these neurons and specific down-regulation of the DRD2 and enkephalin. This specific phenotype of mutant animals is likely due to preferential TrkB expression in DRD2 MSNs. These findings suggest that neurotrophins can control the size of neuronal populations in the brain by promoting the survival of newborn neurons before they migrate to their final destinations.