Transcription Factors Sox5 and Sox6 Exert Direct and Indirect Influences on Oligodendroglial Migration in Spinal Cord and Forebrain
Transcription Factors Sox5 and Sox6 Exert Direct and Indirect Influences on Oligodendroglial Migration in Spinal Cord and Forebrain
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DOI：
10.1002/glia.22919
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发表时间：
2016-01-01
期刊：
影响因子：
6.2
通讯作者：
Stolt, C. Claus
中科院分区：
文献类型：
--
作者：
Baroti, Tina;Zimmermann, Yvonne;Stolt, C. Claus
SoxD蛋白家族的转录因子先前已被证明可以防止发育中的脊髓中少突胶质细胞祖细胞的早熟特化和终末分化。使用在中枢神经系统中特异性缺失SoxD蛋白Sox 5和Sox 6的小鼠，我们现在表明SoxD蛋白还影响脊髓和前脑中少突胶质细胞祖细胞的迁移。在突变小鼠中，少突胶质细胞祖细胞从脑室区和外套膜区的定植的迁移显着延迟，可能是因为减少表达的Pdgf受体α和减少对Pdgf-A作为主要迁移线索的反应。除了这种对Pdgf受体α表达的直接细胞自主作用外，SoxD蛋白还通过使细胞保持未分化状态并防止其迁移能力的过早丧失来促进少突胶质细胞迁移。这种间接作用在胚胎晚期和出生后早期的少突胶质细胞发育阶段变得特别重要。最后，我们发现，Sox 5和Sox 6与Sox 9和Sox 10合作，激活Pdgf受体α的表达，从而维持少突胶质细胞祖细胞在未成熟状态。这与它们在髓磷脂基因上的行为形成对比，在髓磷脂基因上它们拮抗SoxE蛋白的功能。它认为，SoxD蛋白可以作为阻遏物或作为SoxE蛋白的共激活剂，从而以阶段特异性的方式调节它们的功能。
Transcription factors of the SoxD protein family have previously been shown to prevent precocious specification and terminal differentiation of oligodendrocyte progenitor cells in the developing spinal cord. Using mice with specific deletion of the SoxD proteins Sox5 and Sox6 in the central nervous system, we now show that SoxD proteins additionally influence migration of oligodendrocyte progenitors in the spinal cord as well as in the forebrain. In mutant mice, emigration of oligodendrocyte progenitors from the ventricular zone and colonization of the mantle zone are significantly delayed probably because of reduced expression of Pdgf receptor alpha and decreased responsiveness toward Pdgf-A as a main migratory cue. In addition to this direct cell-autonomous effect on Pdgf receptor alpha expression, SoxD proteins furthermore promote oligodendroglial migration by keeping the cells in an undifferentiated state and preventing a premature loss of their migratory capacity. This indirect effect becomes particularly important during late embryonic and early postnatal phases of oligodendroglial development. Finally, we show that Sox5 and Sox6 cooperate with Sox9 and Sox10 to activate Pdgf receptor alpha expression and thereby maintain oligodendrocyte progenitors in the immature state. This contrasts with their behavior on myelin genes where they antagonize the function of SoxE proteins. It argues that SoxD proteins can function either as repressors or as co-activators of SoxE proteins thereby modulating their function in a stage-specific manner.