Adult neurogenesis requires Smad4-mediated bone morphogenic protein signaling in stem cells
Adult neurogenesis requires Smad4-mediated bone morphogenic protein signaling in stem cells
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DOI：
10.1523/jneurosci.4374-07.2008
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发表时间：
2008-01-09
影响因子：
5.3
通讯作者：
Goetz, Magdalena
中科院分区：
文献类型：
--
作者：
Colak, Dilek;Mori, Tetsuji;Goetz, Magdalena
在哺乳动物的大脑中，神经发生仅在前脑的少数区域继续。然而，在这些独特的神经原性小生境中控制神经发生的分子信号仍然不清楚。在这里，我们表明，骨形态发生蛋白（BMP）介导的信号是活跃的成年神经干细胞，是至关重要的启动成年小鼠室管膜下区的神经谱系。成年神经干细胞中Smad4的条件性缺失严重损害神经发生，这是通过输注Noggin（一种BMP的细胞外拮抗剂）进行表型复制的。在干细胞中而不是祖细胞中的Smad4缺失以及Noggin输注导致迁移到胼胝体并分化成少突胶质细胞的Olig2表达后代的数量增加。移植实验进一步验证了这种表型的细胞自主性。因此，BMP介导的信号通过Smad4是必需的，以启动神经干细胞的神经发生和抑制少突胶质细胞的替代命运。
In the mammalian brain, neurogenesis continues only in few regions of the forebrain. The molecular signals governing neurogenesis in these unique neurogenic niches, however, are still ill defined. Here, we show that bone morphogenic protein (BMP)-mediated signaling is active in adult neural stem cells and is crucial to initiate the neurogenic lineage in the adult mouse subependymal zone. Conditional deletion of Smad4 in adult neural stem cells severely impairs neurogenesis, and this is phenocopied by infusion of Noggin, an extracellular antagonist of BMP. Smad4 deletion in stem, but not progenitor cells, as well as Noggin infusion lead to an increased number of Olig2-expressing progeny that migrate to the corpus callosum and differentiate into oligodendrocytes. Transplantation experiments further verified the cell-autonomous nature of this phenotype. Thus, BMP-mediated signaling via Smad4 is required to initiate neurogenesis from adult neural stem cells and suppress the alternative fate of oligodendrogliogenesis.