Laminin regulates postnatal oligodendrocyte production by promoting oligodendrocyte progenitor survival in the subventricular zone.
Laminin regulates postnatal oligodendrocyte production by promoting oligodendrocyte progenitor survival in the subventricular zone.
复制标题
作者：
Relucio J;Menezes MJ;Miyagoe-Suzuki Y;Takeda S;Colognato H
层粘连蛋白家族的细胞外基质蛋白在胚胎脑发育过程中广泛表达，但在脑室和硬膜表面表达丰富，在皮质形成过程中，层粘连蛋白介导放射状胶质细胞附着。然而，在成人脑中，层粘连蛋白的分布是有限的，但发现在血管基板和相关的脑室区(VZ)-脑室下区(SVZ)干细胞壁龛中，层粘连蛋白调节成人神经前体细胞的增殖。然而，目前尚不清楚层粘连蛋白是否调节发生在新生儿/出生后早期VZ-SVZ的少突胶质细胞形成波。在这里，我们报道了编码层粘连蛋白α2亚基的基因Lama2，它调控着出生后的少突胶质细胞发生。在出生时，Lama2−/−小鼠背侧SVZ的少突胶质祖细胞生发区中死亡的少突胶质祖细胞(OPC)水平显著较高。这转化为较少的OPC，无论是在SVZ的背侧，还是在邻近的发育中的白质束--穹隆体部。此外，在Lama2−/−VZ-SVZ内产生OPC的中间前体细胞被错误定位并在靠近脑室表面的地方增殖。随后，在Lama2的−/−部位观察到少突胶质细胞成熟延迟(伴随着OPC堆积)，导致出生后第21天髓鞘功能障碍。总之，这些数据表明，在发育中的出生后VZ-SVZ生发区中，亲生存的层粘连蛋白相互作用调节着少突胶质细胞适当产生的能力或时机。
The laminin family of extracellular matrix proteins are expressed broadly during embryonic brain development, but are enriched at ventricular and pial surfaces where laminins mediate radial glial attachment during corticogenesis. In the adult brain, however, laminin distribution is restricted, yet is found within the vascular basal lamina and associated fractones of the ventricular zone (VZ)-subventricular zone (SVZ) stem cell niche, where laminins regulate adult neural progenitor cell proliferation. It remains unknown, however, if laminins regulate the wave of oligodendrogenesis that occurs in the neonatal/early postnatal VZ-SVZ. Here we report that Lama2, the gene that encodes the laminin α2-subunit, regulates postnatal oligodendrogenesis. At birth, Lama2−/− mice had significantly higher levels of dying oligodendrocyte progenitor cells (OPCs) in the OPC germinal zone of the dorsal SVZ. This translated into fewer OPCs, both in the dorsal SVZ well as in an adjacent developing white matter tract, the corpus callosum. In addition, intermediate progenitor cells that give rise to OPCs in the Lama2−/− VZ-SVZ were mislocalized and proliferated nearer to the ventricle surface. Later, delays in oligodendrocyte maturation (with accompanying OPC accumulation), were observed in the Lama2−/− corpus callosum, leading to dysmyelination by postnatal day 21. Together these data suggest that pro-survival laminin interactions in the developing postnatal VZ-SVZ germinal zone regulate the ability, or timing, of oligodendrocyte production to occur appropriately.
登录
查看更多内容
影响因子：
4.6
作者：
Campos, LS;Leone, DP;ffrench-Constant, C
通讯作者：
ffrench-Constant, C
影响因子：
5.3
作者：
Kazanis, Ilias;Lathia, Justin D.;Ffrench-Constant, Charles
通讯作者：
Ffrench-Constant, Charles
影响因子：
5.2
作者：
Allamand, V;Guicheney, P
通讯作者：
Guicheney, P
影响因子：
19.7
作者：
Leite, CC;Reed, UC;Cerri, GG
通讯作者：
Cerri, GG
影响因子：
4
作者：
Leone, DP;Relvas, JB;Suter, U
通讯作者：
Suter, U