Migration of Oligodendrocyte Progenitor Cells Is Controlled by Transforming Growth Factor β Family Proteins during Corticogenesis
Migration of Oligodendrocyte Progenitor Cells Is Controlled by Transforming Growth Factor β Family Proteins during Corticogenesis
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DOI：
10.1523/jneurosci.1156-14.2014
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发表时间：
2014-11-05
影响因子：
5.3
通讯作者：
Pleasure, Samuel J.
中科院分区：
文献类型：
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作者：
Choe, Youngshik;Huynh, Trung;Pleasure, Samuel J.
在胚胎发育过程中，少突胶质前体细胞（OPCs）首先在前脑腹侧产生，然后向背侧迁移，占据大脑皮层。引导这条迁徙路线的分子线索目前还完全未知。本研究表明，在小鼠胚胎阶段，脑膜和周细胞产生的骨形态发生蛋白-4 （Bmp4）、Bmp7和Tgf β 1将腹侧OPCs排斥到皮层中。在OPC进入皮质之前，Bmp或Tgf β 1信号的异位激活阻碍了OPC向皮质区域的迁移。没有Smad4信号分子的OPCs也不能有效迁移到皮层，并在腹侧区域形成异位。有条件地抑制间充质细胞Tgf β 1或Bmp的表达也显著减少了OPC向皮层的迁移。这些数据表明，间充质Tgf β家族蛋白在皮质发生过程中促进腹侧OPCs向皮质迁移。
During embryonic development oligodendrocyte precursor cells (OPCs) are generated first in the ventral forebrain and migrate dorsally to occupy the cortex. The molecular cues that guide this migratory route are currently completely unknown. Here, we show that bone morphogenetic protein-4 (Bmp4), Bmp7, and Tgf beta 1 produced by the meninges and pericytes repelled ventral OPCs into the cortex at mouse embryonic stages. Ectopic activation of Bmp or Tgf beta 1 signaling before the entrance of OPCs into the cortex hindered OPC migration into the cortical areas. OPCs without Smad4 signaling molecules also failed to migrate into the cortex efficiently and formed heterotopia in ventral areas. OPC migration into the cortex was also dramatically reduced by conditional inhibition of Tgf beta 1 or Bmp expression from mesenchymal cells. The data suggest that mesenchymal Tgf beta family proteins promote migration of ventral OPCs into the cortex during corticogenesis.