Krox-20 controls SCIP expression, cell cycle exit and susceptibility to apoptosis in developing myelinating Schwann cells.
Krox-20 controls SCIP expression, cell cycle exit and susceptibility to apoptosis in developing myelinating Schwann cells.
复制标题
Krox-20 控制发育中的有髓鞘雪旺细胞的 SCIP 表达、细胞周期退出和细胞凋亡的易感性。
作者：
T. Zorick;D. Syroid;Adrienne M. Brown;Tom Gridley;G. Lemke
转录因子Krox-20和SCIP各自在雪旺细胞的分化中发挥重要作用。然而，编码这两种蛋白质的基因表现出不同的表达时程，并在突变时产生不同的细胞表型。SCIP在Krox-20最初出现之前表达，并且在髓鞘形成和非髓鞘形成的雪旺细胞谱系中都是瞬时的;而相比之下，Krox-20在SCIP后约24小时出现，然后仅在髓鞘形成谱系中出现，其中其表达稳定地维持到成年期。类似地，SCIP-/-雪旺细胞的分化似乎在髓鞘形成之前的早髓鞘形成阶段暂时停滞，而Krox-20（-/-）细胞根据形态学标准在该阶段被阻止。这些观察结果使我们研究了Krox-20小鼠突变体中的SCIP调节和许旺细胞表型。我们发现，在Krox-20（-/-）雪旺细胞中，SCIP的表达从短暂转化为持续。我们进一步观察到，雪旺细胞增殖和凋亡，这是SCIP+细胞的正常特征，也显着增加出生后发育后期Krox-20突变体相对于野生型，细胞分裂和凋亡的水平是平衡的，以产生稳定数量的雪旺细胞在外周神经内。这些数据表明，在髓鞘形成的雪旺细胞中Krox-20的损失在髓鞘形成阶段阻止分化，如通过SCIP表达、有丝分裂活性和对细胞凋亡的敏感性所评估的。
The transcription factors Krox-20 and SCIP each play important roles in the differentiation of Schwann cells. However, the genes encoding these two proteins exhibit distinct time courses of expression and yield distinct cellular phenotypes upon mutation. SCIP is expressed prior to the initial appearance of Krox-20, and is transient in both the myelinating and non-myelinating Schwann cell lineages; while in contrast, Krox-20 appears approximately 24 hours after SCIP and then only within the myelinating lineage, where its expression is stably maintained into adulthood. Similarly, differentiation of SCIP-/- Schwann cells appears to transiently stall at the promyelinating stage that precedes myelination, whereas Krox-20(-/-) cells are, by morphological criteria, arrested at this stage. These observations led us to examine SCIP regulation and Schwann cell phenotype in Krox-20 mouse mutants. We find that in Krox-20(-/-) Schwann cells, SCIP expression is converted from transient to sustained. We further observe that both Schwann cell proliferation and apoptosis, which are normal features of SCIP+ cells, are also markedly increased late in postnatal development in Krox-20 mutants relative to wild type, and that the levels of cell division and apoptosis are balanced to yield a stable number of Schwann cells within peripheral nerves. These data demonstrate that the loss of Krox-20 in myelinating Schwann cells arrests differentiation at the promyelinating stage, as assessed by SCIP expression, mitotic activity and susceptibility to apoptosis.
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影响因子：
56.9
作者：
MONUKI, ES;KUHN, R;LEMKE, G
通讯作者：
LEMKE, G
影响因子：
4.6
作者：
E. Collarini;R. Kuhn;Caroline J. Marshall;E. Monuki;Greg Lemke;William D. Richardson
通讯作者：
E. Collarini;R. Kuhn;Caroline J. Marshall;E. Monuki;Greg Lemke;William D. Richardson
缺乏神经营养素受体 p75 的小鼠的基底前脑神经元损失。
DOI：
10.1126/science.277.5327.837
发表时间：
1997
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Peterson,DA;Leppert,JT;Lee,KF;Gage,FH
通讯作者：
Gage,FH
小鼠外周髓鞘蛋白零基因的 DNA 序列、基因组组织和染色体定位：多态性等位基因的鉴定。
影响因子：
4.4
作者：
You,KH;Hsieh,CL;Hayes,C;Stahl,N;Francke,U;Popko,B
通讯作者：
Popko,B