Distinct levels of Notch activity for commitment and terminal differentiation of stem cells in the adult fly intestine
Distinct levels of Notch activity for commitment and terminal differentiation of stem cells in the adult fly intestine
复制标题
DOI：
10.1242/dev.065292
复制
发表时间：
2011-11-01
期刊：
影响因子：
4.6
通讯作者：
Bardin, Allison J.
中科院分区：
文献类型：
--
作者：
Perdigoto, Carolina N.;Schweisguth, Francois;Bardin, Allison J.
对成体干细胞自我更新和分化的严格调控确保组织得到适当的维持。在果蝇肠道中，Notch信号控制着承诺(即退出自我更新)和末端分化。在这里，我们证明了对Notch活性的不同要求：承诺需要较高的Notch活性，而较低的Notch活性可以发生末端分化。我们鉴定了Notch信号的调节者GDP-甘露糖4，6-脱水酶(GMD)基因，它是蛋白质合成所必需的，但对末端分化是必不可少的。GMD缺失会导致异常的、自我更新的干细胞分裂，导致额外的ISC样细胞在Notch报告程序激活方面存在缺陷，以及野生型样细胞分裂产生正确的末端分化细胞。使用额外的遗传方法降低Notch信号，我们提供了进一步的证据，表明承诺比末端分化对Notch信号的要求更高。我们的工作表明，对高水平Notch活性的承诺要求保护干细胞不会通过分化而丢失，揭示了Notch信号水平在该系统中的重要性的新作用。
Tight regulation of self-renewal and differentiation of adult stem cells ensures that tissues are properly maintained. In the Drosophila intestine, both commitment, i.e. exit from self-renewal, and terminal differentiation are controlled by Notch signaling. Here, we show that distinct requirements for Notch activity exist: commitment requires high Notch activity, whereas terminal differentiation can occur with lower Notch activity. We identified the gene GDP-mannose 4,6-dehydratase (Gmd), a modulator of Notch signaling, as being required for commitment but dispensable for terminal differentiation. Gmd loss resulted in aberrant, self-renewing stem cell divisions that generated extra ISC-like cells defective in Notch reporter activation, as well as wild-type-like cell divisions that produced properly terminally differentiated cells. Lowering Notch signaling using additional genetic means, we provided further evidence that commitment has a higher Notch signaling requirement than terminal differentiation. Our work suggests that a commitment requirement for high-level Notch activity safeguards the stem cells from loss through differentiation, revealing a novel role for the importance of Notch signaling levels in this system.