TGFβ type II receptor signaling controls Schwann cell death and proliferation in developing nerves
TGFβ type II receptor signaling controls Schwann cell death and proliferation in developing nerves
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DOI：
10.1523/jneurosci.1578-06.2006
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发表时间：
2006-08-15
影响因子：
5.3
通讯作者：
Jessen, Kristjan R.
中科院分区：
文献类型：
--
作者：
D'Antonio, Maurizio;Droggiti, Anna;Jessen, Kristjan R.
在发育过程中，雪旺细胞的数量被精确地调整以匹配轴突的数量。目前还不清楚哪些生长因子或受体在体内进行这种重要的控制。在这里，我们测试了II型转化生长因子（TGF）β受体是否在这一过程中发挥作用。我们产生了一种条件性基因敲除小鼠，其中II型TGF β受体仅在许旺细胞中特异性消融。失活的受体，明显至少从胚胎的第18天，导致在正常发育和受损的神经抑制雪旺细胞死亡。值得注意的是，突变体还显示出施万细胞增殖的强烈减少。因此，野生型和突变型神经中的雪旺细胞数量保持相似。TGF β信号传导的缺乏似乎并不影响以前涉及TGF β的其他过程，包括髓鞘形成和成年神经对损伤的反应。这是生长因子受体参与促进发育过程中许旺细胞分裂的第一个体内证据，也是控制正常发育许旺细胞死亡的受体的第一个遗传证据。
During development, Schwann cell numbers are precisely adjusted to match the number of axons. It is essentially unknown which growth factors or receptors carry out this important control in vivo. Here, we tested whether the type II transforming growth factor (TGF)beta receptor has a role in this process. We generated a conditional knock-out mouse in which the type II TGF beta receptor is specifically ablated only in Schwann cells. Inactivation of the receptor, evident at least from embryonic day 18, resulted in suppressed Schwann cell death in normally developing and injured nerves. Notably, the mutants also showed a strong reduction in Schwann cell proliferation. Consequently, Schwann cell numbers in wild-type and mutant nerves remained similar. Lack of TGF beta signaling did not appear to affect other processes in which TGF beta had been implicated previously, including myelination and response of adult nerves to injury. This is the first in vivo evidence for a growth factor receptor involved in promoting Schwann cell division during development and the first genetic evidence for a receptor that controls normal developmental Schwann cell death.