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Sprouty2 regulates positioning of retinal progenitors through suppressing the Ras/Raf/MAPK pathway

Sproutys are negative regulators of the Ras/Raf/MAPK signaling pathway and involved in regulation of organogenesis, differentiation, cell migration and proliferation. Although the function of Sproutys have been extensively studied during embryonic development, their role and mode of action during ey...

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Autores principales: Sun, Jian, Yoon, Jaeho, Lee, Moonsup, Hwang, Yoo-Seok, Daar, Ira O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426826/
https://www.ncbi.nlm.nih.gov/pubmed/32792568
http://dx.doi.org/10.1038/s41598-020-70670-2
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author Sun, Jian
Yoon, Jaeho
Lee, Moonsup
Hwang, Yoo-Seok
Daar, Ira O.
author_facet Sun, Jian
Yoon, Jaeho
Lee, Moonsup
Hwang, Yoo-Seok
Daar, Ira O.
author_sort Sun, Jian
collection PubMed
description Sproutys are negative regulators of the Ras/Raf/MAPK signaling pathway and involved in regulation of organogenesis, differentiation, cell migration and proliferation. Although the function of Sproutys have been extensively studied during embryonic development, their role and mode of action during eye formation in vertebrate embryonic development is still unknown. Here we show that Xenopus sprouty2 is expressed in the optic vesicle at late neurula stage and knockdown of Sprouty2 prevents retinal progenitors from populating the retina, which in turn gives rise to small eyes. In the absence of Sprouty2, progenitor cell population of the retina can be restored by blocking the MAPK signaling pathway through overexpression of DN-Ras or DN-Raf. In contrast, activation of the MAPK pathway through overexpression of a constitutively active form of c-Raf (ca-Raf) inhibits progenitor population of the retina, similar to the Sprouty2 loss-of-function phenotype. Moreover, we present evidence that the retinal defect observed in Sprouty2 morphants is attributed to the failure of proper movement of retinal progenitors into the optic vesicle, rather than an effect on progenitor cell survival. These results suggest that Sprouty2 is required for the positioning of retinal progenitors within the optic vesicle through suppressing Ras/Raf/MAPK signaling pathway.
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spelling pubmed-74268262020-08-14 Sprouty2 regulates positioning of retinal progenitors through suppressing the Ras/Raf/MAPK pathway Sun, Jian Yoon, Jaeho Lee, Moonsup Hwang, Yoo-Seok Daar, Ira O. Sci Rep Article Sproutys are negative regulators of the Ras/Raf/MAPK signaling pathway and involved in regulation of organogenesis, differentiation, cell migration and proliferation. Although the function of Sproutys have been extensively studied during embryonic development, their role and mode of action during eye formation in vertebrate embryonic development is still unknown. Here we show that Xenopus sprouty2 is expressed in the optic vesicle at late neurula stage and knockdown of Sprouty2 prevents retinal progenitors from populating the retina, which in turn gives rise to small eyes. In the absence of Sprouty2, progenitor cell population of the retina can be restored by blocking the MAPK signaling pathway through overexpression of DN-Ras or DN-Raf. In contrast, activation of the MAPK pathway through overexpression of a constitutively active form of c-Raf (ca-Raf) inhibits progenitor population of the retina, similar to the Sprouty2 loss-of-function phenotype. Moreover, we present evidence that the retinal defect observed in Sprouty2 morphants is attributed to the failure of proper movement of retinal progenitors into the optic vesicle, rather than an effect on progenitor cell survival. These results suggest that Sprouty2 is required for the positioning of retinal progenitors within the optic vesicle through suppressing Ras/Raf/MAPK signaling pathway. Nature Publishing Group UK 2020-08-13 /pmc/articles/PMC7426826/ /pubmed/32792568 http://dx.doi.org/10.1038/s41598-020-70670-2 Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2020 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Sun, Jian
Yoon, Jaeho
Lee, Moonsup
Hwang, Yoo-Seok
Daar, Ira O.
Sprouty2 regulates positioning of retinal progenitors through suppressing the Ras/Raf/MAPK pathway
title Sprouty2 regulates positioning of retinal progenitors through suppressing the Ras/Raf/MAPK pathway
title_full Sprouty2 regulates positioning of retinal progenitors through suppressing the Ras/Raf/MAPK pathway
title_fullStr Sprouty2 regulates positioning of retinal progenitors through suppressing the Ras/Raf/MAPK pathway
title_full_unstemmed Sprouty2 regulates positioning of retinal progenitors through suppressing the Ras/Raf/MAPK pathway
title_short Sprouty2 regulates positioning of retinal progenitors through suppressing the Ras/Raf/MAPK pathway
title_sort sprouty2 regulates positioning of retinal progenitors through suppressing the ras/raf/mapk pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426826/
https://www.ncbi.nlm.nih.gov/pubmed/32792568
http://dx.doi.org/10.1038/s41598-020-70670-2
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