Spred negatively regulates lens growth by modulating epithelial cell proliferation and fiber differentiation

Spred negatively regulates lens growth by modulating epithelial cell proliferation and fiber differentiation.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1016/j.exer.2018.09.019
Journal or Publication Title: Experimental Eye Research
Volume: 178
Page Range: pp. 160-175
Date: 2019
Divisions: Gene and Stem Cell Therapy
Depositing User: General Admin
Identification Number: 10.1016/j.exer.2018.09.019
ISSN: 00144835
Date Deposited: 21 Dec 2020 05:54

Spred, like Sprouty (Spry) and also Sef proteins, have been identified as important regulators of receptor tyrosine kinase (RTK)-mediated MAPK/ERK-signaling in various developmental systems, controlling cellular processes such as proliferation, migration and differentiation. Spreds are widely expressed during early embryogenesis, and in the eye lens, become more localised in the lens epithelium with later development, overlapping with other antagonists including Spry. Given the synexpression of Spreds and Spry in lens, in order to gain a better understanding of their specific roles in regulating growth factor mediated-signaling and cell behavior, we established and characterised lines of transgenic mice overexpressing Spred1 or Spred2, specifically in the lens. This overexpression of Spreds resulted in a small lens phenotype during ocular morphogenesis, retarding its growth by compromising epithelial cell proliferation and fiber differentiation. These in situ findings were shown to be dependent on the ability of Spreds to suppress MAPK-signaling, in particular FGF-induced ERK1/2-signaling in lens cells. This was validated in vitro using lens epithelial explants, that highlighted the overlapping role of Spreds with Spry2, but not Spry1. This study provides insights into the putative function of Spreds and Spry in situ, some overlapping and some distinct, and their importance in regulating lens cell proliferation and fiber differentiation contributing to lens and eye growth.

Keywords: Development; ERK1/2; FGF; Fiber differentiation; Lens epithelial cell proliferation; Spred; Sprouty.

Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Susanto, Alyssa
Zhao, Guannan
Wazin, Fatima
Feng, Yue
Rasko, John E.J.
Bailey, Charles G.
Lovicu, Frank J.
Last Modified: 21 Dec 2020 05:54
URI: https://eprints.centenary.org.au/id/eprint/315

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