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

  1. Ankur Garg
  2. Abdul Hannan
  3. Qian Wang
  4. Neoklis Makrides
  5. Jian Zhong
  6. Hongge Li
  7. Sungtae Yoon
  8. Yingyu Mao
  9. Xin Zhang  Is a corresponding author
  1. Columbia University, United States
  2. 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).

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Ankur Garg

    Departments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Abdul Hannan

    Departments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Qian Wang

    Department of Ophthalmology, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Neoklis Makrides

    Department of Ophthalmology, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jian Zhong

    Burke Medical Research Institute, Weill Cornell Medical College, White Plains, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Hongge Li

    Department of Ophthalmology, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Sungtae Yoon

    Department of Ophthalmology, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Yingyu Mao

    Departments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Xin Zhang

    Department of Ophthalmology, Columbia University, New York, United States
    For correspondence
    xz2369@columbia.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5555-0825

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.

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.

Reviewing Editor

  1. Ivan Topisirovic, Jewish General Hospital, Canada

Publication history

  1. Received: September 16, 2019
  2. Accepted: February 10, 2020
  3. Accepted Manuscript published: February 11, 2020 (version 1)
  4. 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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  1. Ankur Garg
  2. Abdul Hannan
  3. Qian Wang
  4. Neoklis Makrides
  5. Jian Zhong
  6. Hongge Li
  7. Sungtae Yoon
  8. Yingyu Mao
  9. Xin Zhang
(2020)
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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