Crk proteins transduce FGF signaling to promote lens fiber cell elongation
- Columbia University, United States
- University of California, San Diego, United States
- Texas A&M, United States
- Indiana University School of Medicine, United States
- Third Military Medical University, China
- Children's Mercy Kansas City, United States
Abstract
Specific cell shapes are fundamental to the organization and function of multicellular organisms. Fibroblast Growth Factor (FGF) signaling induces the elongation of lens fiber cells during vertebrate lens development. Nonetheless, exactly how this extracellular FGF signal is transmitted to the cytoskeletal network has previously not been determined. Here, we show that the Crk family of adaptor proteins, Crk and Crkl, are required for mouse lens morphogenesis but not differentiation. Genetic ablation and epistasis experiments demonstrated that Crk and Crkl play overlapping roles downstream of FGF signaling in order to regulate lens fiber cell elongation. Upon FGF stimulation, Crk proteins were found to interact with Frs2, Shp2 and Grb. The loss of Crk proteins was partially compensated for by the activation of Ras and Rac signaling. These results reveal that Crk proteins are important partners of the Frs2/Shp2/Grb2 complex in mediating FGF signaling, specifically promoting cell shape changes.
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Author details
Funding
National Eye Institute (EY017061)
- Tamica N Collins
- Yingyu Mao
- Hongge Li
- Angela Hong
- Xin Zhang
National Eye Institute (5P30EY019007)
- Xin Zhang
Research to Prevent Blindness (Jules and Doris Stein professorship)
- Xin Zhang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Mouse maintenance and experimentation was performed according to protocols approved by Columbia University Institutional Animal Care and Use Committee (protocol AAAR0429).
Copyright
© 2018, Collins 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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Crk proteins transduce FGF signaling to promote lens fiber cell elongation
eLife 7:e32586.
https://doi.org/10.7554/eLife.32586
