Etv transcription factors functionally diverge from their upstream FGF signaling in lens development
- Columbia University, United States
- Weill Cornell Medical College, United States
Abstract
The signal regulated transcription factors (SRTFs) control the ultimate transcriptional output of signaling pathways. Here, we examined a family of FGF-induced SRTFs – Etv1, Etv 4, and Etv 5 – in murine lens development. Contrary to FGF receptor mutants that displayed loss of ERK signaling and defective cell differentiation, Etv 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 Tsc2 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.
Data availability
The RNAseq data are available from the GEO repository (GSE137215).
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RNA-seq of the lens transition zone in control vs Pea3-depleted mouse embryonic tissueNCBI Gene Expression Omnibus, GSE137215.
Article and author information
Author details
Funding
National Eye Institute (EY017061)
- Xin Zhang
National Eye Institute (EY025933)
- Xin Zhang
Research to Prevent Blindness (Jules and Doris Stein Research to Prevent Blindness Professorship)
- Xin Zhang
Starr Foundation (Graduate fellowship)
- Ankur Garg
Natural Sciences and Engineering Research Council of Canada (Postdoctoral fellowship)
- Qian Wang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Ivan Topisirovic, Jewish General Hospital, Canada
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocol (AABD8562) of Columbia University Medical Center.
Version history
- Received: September 16, 2019
- Accepted: February 10, 2020
- Accepted Manuscript published: February 11, 2020 (version 1)
- Version of Record published: March 13, 2020 (version 2)
Copyright
© 2020, Garg et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Etv transcription factors functionally diverge from their upstream FGF signaling in lens development
eLife 9:e51915.
https://doi.org/10.7554/eLife.51915
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