Fmrp regulates oligodendrocyte lineage cell specification and differentiation.
Fmrp regulates oligodendrocyte lineage cell specification and differentiation.
复制标题
作者：
Doll CA;Scott K;Appel B
神经发育需要各种神经元和神经胶质细胞类型的精确整合。在早期胚胎发育过程中，运动神经元和少突胶质细胞前体细胞（OPC）是由位于脊髓脑室周围pMN祖细胞结构域的神经祖细胞指定的。胶质细胞生成后，OPCs可以分化为少突胶质细胞（OLs）-中枢神经系统的髓鞘神经胶质细胞-或保持OPCs。为了产生能够高度分化功能的独特细胞类型，这些特化和分化事件需要专门的基因表达程序。RNA结合蛋白（RBP）调节发育中神经系统的mRNA定位和翻译，并与许多神经发育障碍有关。一个例子是脆性X综合征（FXS），由RBP脆性X智力低下蛋白（FMRP）的丢失引起。重要的是，患有FXS的婴儿的白色物质减少，我们先前表明，斑马鱼Fmrp是OLs自主需要的，以促进髓鞘生长。我们现在发现，Fmrp调节pMN祖细胞中的细胞特化，使得fmr1突变的斑马鱼产生更少的运动神经元和过量的OPCs。FMRP随后促进OPCs的分化，导致在fmr1幼虫的发育中的脊髓中分化的OL较少。虽然脊髓祖域的早期模式出现在很大程度上正常fmr1突变体在早期胚胎发生，Shh信号大大减少。两者合计，这些结果表明FMRP在少突胶质细胞系细胞的规范和分化中的细胞阶段特异性要求。
Neurodevelopment requires the precise integration of a wide variety of neuronal and glial cell types. During early embryonic development, motor neurons and then oligodendrocyte precursor cells (OPCs) are specified from neural progenitors residing in the periventricular pMN progenitor domain of the spinal cord. Following gliogenesis, OPCs can differentiate as oligodendrocytes (OLs)–the myelinating glial cells of the central nervous system–or remain as OPCs. To generate unique cell types capable of highly divergent functions, these specification and differentiation events require specialized gene expression programs. RNA binding proteins (RBPs) regulate mRNA localization and translation in the developing nervous system and are linked to many neurodevelopmental disorders. One example is Fragile X syndrome (FXS), caused by the loss of the RBP fragile X mental retardation protein (FMRP). Importantly, infants with FXS have reduced white matter and we previously showed that zebrafish Fmrp is autonomously required in OLs to promote myelin sheath growth. We now find that Fmrp regulates cell specification in pMN progenitor cells such that fmr1 mutant zebrafish generate fewer motor neurons and excess OPCs. Fmrp subsequently promotes differentiation of OPCs, leading to fewer differentiating OLs in the developing spinal cord of fmr1 larvae. Although the early patterning of spinal progenitor domains appears largely normal in fmr1 mutants during early embryogenesis, Shh signaling is greatly diminished. Taken together, these results suggest cell stage-specific requirements for Fmrp in the specification and differentiation of oligodendrocyte lineage cells.
登录
查看更多内容
影响因子：
4.5
作者：
Hornig J;Fröb F;Vogl MR;Hermans-Borgmeyer I;Tamm ER;Wegner M
通讯作者：
Wegner M
影响因子：
64.8
作者：
Bergles, DE;Roberts, JDB;Jahr, CE
通讯作者：
Jahr, CE
影响因子：
2.5
作者：
KIMMEL, CB;BALLARD, WW;SCHILLING, TF
通讯作者：
SCHILLING, TF
影响因子：
4.6
作者：
Al Oustah, Amir;Danesin, Cathy;Soula, Cathy
通讯作者：
Soula, Cathy
影响因子：
4.6
作者：
Doll, Caleb A.;Broadie, Kendal
通讯作者：
Broadie, Kendal