Bone morphogenetic proteins negatively control oligodendrocyte precursor specification in the chick spinal cord.
Bone morphogenetic proteins negatively control oligodendrocyte precursor specification in the chick spinal cord.
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发表时间：
2002-11
期刊：
影响因子：
4.6
通讯作者：
Soraya Mekki-Dauriac;E. Agius;P. Kan;P. Cochard
中科院分区：
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作者：
Soraya Mekki-Dauriac;E. Agius;P. Kan;P. Cochard
在脊椎动物脊髓中，少突胶质细胞起源于腹侧神经上皮的限制区域。这种腹侧定位的少突胶质细胞前体（OLPs）依赖于腹侧中线细胞分泌的音刺猬（Shh）的诱导影响。我们已经调查了OLP规格的腹侧限制是否也可能依赖于骨形态发生蛋白（BMP）介导的抑制信号。骨形成蛋白总是显着抑制腹侧神经组织中的少突胶质细胞的发育，在体外和体内。相反，在体内消融的最背侧部分的鸡脊髓或使用头蛋白产生细胞的移植物的BMP信号的失活促进神经上皮OLP背侧的出现，其正常的域的出现，显示内源性BMP有助于抑制少突胶质细胞的发育在脊髓。骨形态发生蛋白能够反对Shh介导的诱导OLP在脊髓神经上皮外植体解剖前少突胶质细胞诱导，这表明骨形态发生蛋白可能抑制OLP规格通过干扰Shh信号在体内。引人注目的是，在参与OLP规范的转录因子中，BMP处理强烈抑制Olig2的表达，但不抑制Nkx2.2的表达，这表明BMP介导的对少突胶质细胞生成的抑制是通过抑制前转录因子来控制的。总之，我们的数据表明，少突分化不仅是由腹诱导信号，如嘘，但也由背抑制信号，包括BMP因子。他们认为OLP的背腹侧位置取决于Shh和BMP活性之间的严格调节平衡。
In the vertebrate spinal cord, oligodendrocytes originate from a restricted region of the ventral neuroepithelium. This ventral localisation of oligodendrocyte precursors (OLPs) depends on the inductive influence of sonic hedgehog (Shh) secreted by ventral midline cells. We have investigated whether the ventral restriction of OLP specification might also depend on inhibiting signals mediated by bone morphogenetic proteins (BMPs). BMPs invariably and markedly inhibited oligodendrocyte development in ventral neural tissue both in vitro and in vivo. Conversely, in vivo ablation of the dorsal most part of the chick spinal cord or inactivation of BMP signalling using grafts of noggin-producing cells promoted the appearance of neuroepithelial OLPs dorsal to their normal domain of emergence, showing that endogenous BMPs contribute to the inhibition of oligodendrocyte development in the spinal cord. BMPs were able to oppose the Shh-mediated induction of OLPs in spinal cord neuroepithelial explants dissected before oligodendrocyte induction, suggesting that BMPs may repress OLP specification by interfering with Shh signalling in vivo. Strikingly, among the transcription factors involved in OLP specification, BMP treatment strongly inhibited the expression of Olig2 but not of Nkx2.2, suggesting that BMP-mediated inhibition of oligodendrogenesis is controlled through the repression of the former transcription factor. Altogether, our data show that oligodendrogenesis is not only regulated by ventral inductive signals such as Shh, but also by dorsal inhibiting signals including BMP factors. They suggest that the dorsoventral position of OLPs depends on a tightly regulated balance between Shh and BMP activities.