Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Science, University of Portsmouth, St Michael's Building, Portsmouth, United Kingdom.
Glia. 2012 Dec;60(12):1977-90. doi: 10.1002/glia.22413. Epub 2012 Sep 5.
FGF2 is considered a key factor in the generation of oligodendrocytes (OLs) derived from neural stem cells (NSCs) located within the subventricular zone (SVZ). Here, we have examined FGF2 signaling in the forebrain of postnatal and adult mice. Using qPCR of microdissected microdomains of the dorsal SVZ (dSVZ) and lateral SVZ (lSVZ), and prominin1-sorted NSCs purified from these microdomains, we show that transcripts for FGF receptor 1 (FGFR1) and FGFR2 are enriched in the dSVZ, from which OLs are largely derived, whereas FGFR3 are significantly enriched within prominen1-sorted NSC of the lSVZ, which mainly generate olfactory interneurons. We show that direct administration of FGF2 into the lateral ventricle increased the generation of oligodendrocyte progenitors (OPCs) throughout the SVZ, both within the dSVZ and ectopically in the lSVZ and ependymal wall of the SVZ. Furthermore, FGF2 stimulated proliferation of neural progenitors (NPs) and their differentiation into OPCs. The results indicate that FGF2 increased specification of OPCs, inducing NPs to follow an oligodendrocyte developmental pathway. Notably, FGF2 did not block OPC differentiation and increased the number of oligodendrocytes in the periventricular white matter (PVWM) and cortex. However, FGF2 markedly disrupted myelination in the PVWM. A key finding was that FGF2 had equivalent actions on the generation of OPCs and myelin disruption in postnatal and adult mice. This study demonstrates a central role for FGF2 in promoting oligodendrocyte generation in the developing and adult brain.
成纤维细胞生长因子 2（FGF2）被认为是神经干细胞（NSC）分化为少突胶质细胞（OLs）的关键因素，这些 NSC 位于侧脑室下区（SVZ）。在此，我们研究了 FGF2 信号通路在新生和成年小鼠前脑的作用。通过 qPCR 检测背侧 SVZ（dSVZ）和外侧 SVZ（lSVZ）微区的微分离以及从这些微区中分离的 prominin1 分选 NSCs，我们发现 FGF 受体 1（FGFR1）和 FGFR2 的转录本在 dSVZ 中丰富，OLs 主要来源于此；而 FGFR3 在 lSVZ 的 prominin1 分选 NSCs 中显著富集，后者主要产生嗅鞘细胞。我们发现，直接将 FGF2 注射到侧脑室中会增加 SVZ 中 OL 前体细胞（OPC）的产生，包括 dSVZ 中的 OPC 以及异位产生的 lSVZ 和 SVZ 室管膜壁中的 OPC。此外，FGF2 刺激神经前体细胞（NPs）的增殖，并促使其分化为 OPC。结果表明，FGF2 增加了 OPC 的特异性，诱导 NPs 沿着少突胶质细胞发育途径分化。值得注意的是，FGF2 不会阻止 OPC 的分化，并增加脑室周围白质（PVWM）和皮质中的少突胶质细胞数量。然而，FGF2 显著破坏了 PVWM 中的髓鞘形成。一个关键发现是，FGF2 对 OPC 的产生和髓鞘破坏具有同等作用，无论是在新生小鼠还是成年小鼠中。本研究表明，FGF2 在促进发育中和成年大脑中少突胶质细胞的产生中起关键作用。
