Sox10 is required for Schwann cell identity and progression beyond the immature Schwann cell stage.
Sox10 is required for Schwann cell identity and progression beyond the immature Schwann cell stage.
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DOI：
10.1083/jcb.200912142
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发表时间：
2010-05-17
期刊：
影响因子：
--
通讯作者：
Wegner M
中科院分区：
文献类型：
--
作者：
Finzsch M;Schreiner S;Kichko T;Reeh P;Tamm ER;Bösl MR;Meijer D;Wegner M
Sox 10转录因子需要维持以及指定胶质细胞的身份，增加了与Sox 10突变相关的神经病变的新原因。转录因子SOX 10的突变导致神经损伤，包括人类的Waardenburg-Hirschsprung综合征和周围神经病变。这部分归因于Sox 10在早期神经嵴中的存活、多能性的维持和对几种细胞谱系（包括外周神经胶质细胞）的特异性的需要。因此，Sox 10缺陷小鼠中不存在外周神经胶质细胞。有趣的是，Sox 10在特化后继续在这些细胞中表达。为了分析神经胶质细胞的功能后，规范，我们专门删除Sox 10在未成熟的许旺细胞的条件诱变。突变小鼠在出生后第7周前死于周围神经病变。神经改变包括神经束膜鞘变薄，脂质和胶原沉积增加，细胞组成发生显著变化。神经传导也严重异常，既没有髓鞘化也没有非髓鞘化的雪旺细胞形成。相反，不同大小的轴突在大束中保持未分类。雪旺氏细胞无法发育到不成熟阶段，无法保持身份。因此，我们的研究确定了SOX 10突变患者周围神经病变的新原因。
The Sox10 transcription factor is required to maintain as well as specify glial identity, adding new causes for the neuropathies associated with SOX10 mutations. Mutations in the transcription factor SOX10 cause neurocristopathies, including Waardenburg-Hirschsprung syndrome and peripheral neuropathies in humans. This is partly attributed to a requirement for Sox10 in early neural crest for survival, maintenance of pluripotency, and specification to several cell lineages, including peripheral glia. As a consequence, peripheral glia are absent in Sox10-deficient mice. Intriguingly, Sox10 continues to be expressed in these cells after specification. To analyze glial functions after specification, we specifically deleted Sox10 in immature Schwann cells by conditional mutagenesis. Mutant mice died from peripheral neuropathy before the seventh postnatal week. Nerve alterations included a thinned perineurial sheath, increased lipid and collagen deposition, and a dramatically altered cellular composition. Nerve conduction was also grossly aberrant, and neither myelinating nor nonmyelinating Schwann cells formed. Instead, axons of different sizes remained unsorted in large bundles. Schwann cells failed to develop beyond the immature stage and were unable to maintain identity. Thus, our study identifies a novel cause for peripheral neuropathies in patients with SOX10 mutations.
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影响因子：
5.3
作者：
Kuhlbrodt, K;Herbarth, B;Wegner, M
通讯作者：
Wegner, M
DOI：
10.1083/jcb.200109021
发表时间：
2002-01-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Feltri ML;Graus Porta D;Previtali SC;Nodari A;Migliavacca B;Cassetti A;Littlewood-Evans A;Reichardt LF;Messing A;Quattrini A;Mueller U;Wrabetz L
通讯作者：
Wrabetz L
影响因子：
2.7
作者：
Maka, M;Stolt, CC;Wegner, M
通讯作者：
Wegner, M
DOI：
10.1073/pnas.0407836102
发表时间：
2005-02-15
影响因子：
11.1
作者：
Le, N;Nagarajan, R;Milbrandt, J
通讯作者：
Milbrandt, J
DOI：
10.1126/science.1166562
发表时间：
2009-01-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kao SC;Wu H;Xie J;Chang CP;Ranish JA;Graef IA;Crabtree GR
通讯作者：
Crabtree GR