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Etv 转录因子在晶状体发育过程中从其上游的 FGF 信号中功能上分化出来。

Etv transcription factors functionally diverge from their upstream FGF signaling in lens development.

机构信息

Department of Ophthalmology, Columbia University, New York, United States.

Department of Pathology and Cell Biology, Columbia University, New York, United States.

出版信息

Elife. 2020 Feb 11;9:e51915. doi: 10.7554/eLife.51915.

DOI:10.7554/eLife.51915
PMID:32043969
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7069720/
Abstract

The signal regulated transcription factors (SRTFs) control the ultimate transcriptional output of signaling pathways. Here, we examined a family of FGF-induced SRTFs - , , and - in murine lens development. Contrary to FGF receptor mutants that displayed loss of ERK signaling and defective cell differentiation, deficiency augmented ERK phosphorylation without disrupting the normal lens fiber gene expression. Instead, the transitional zone for lens differentiation was shifted anteriorly as a result of reduced Jag1-Notch signaling. We also showed that Etv proteins suppresses mTOR activity by promoting expression, which is necessary for the nuclei clearance in mature lens. These results revealed the functional divergence between Etv and FGF in lens development, demonstrating that these SRTFs can operate outside the confine of their upstream signaling.

摘要

信号调节转录因子（SRTFs）控制着信号通路的最终转录输出。在这里，我们研究了一组 FGF 诱导的 SRTFs—— 、 和 在小鼠晶状体发育中的作用。与显示 ERK 信号丢失和细胞分化缺陷的 FGF 受体突变体相反， 缺乏增强了 ERK 磷酸化，而没有破坏正常的晶状体纤维基因表达。相反，由于 Jag1-Notch 信号的减少，晶状体分化的过渡区向前移位。我们还表明，Etv 蛋白通过促进 的表达来抑制 mTOR 活性，这对于成熟晶状体中的核清除是必需的。这些结果揭示了 Etv 和 FGF 在晶状体发育中的功能分化，表明这些 SRTFs 可以在其上游信号的限制之外发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f18/7069720/495e516ad65e/elife-51915-fig7-figsupp1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f18/7069720/7e10ef29e3ab/elife-51915-fig4.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f18/7069720/aaec4a79f3bc/elife-51915-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f18/7069720/495e516ad65e/elife-51915-fig7-figsupp1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f18/7069720/bf2db17cb4cc/elife-51915-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f18/7069720/50a986bee5a1/elife-51915-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f18/7069720/7e10ef29e3ab/elife-51915-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f18/7069720/91a611903874/elife-51915-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f18/7069720/5808ab5c7e06/elife-51915-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f18/7069720/3a9522bf44dd/elife-51915-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f18/7069720/a4907530ab85/elife-51915-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f18/7069720/aaec4a79f3bc/elife-51915-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f18/7069720/495e516ad65e/elife-51915-fig7-figsupp1.jpg

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