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

Abstract 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...

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Autores principales:	Jian Sun, Jaeho Yoon, Moonsup Lee, Yoo-Seok Hwang, Ira O. Daar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2e1b714265fe4df098176f19f8e89fc2
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spelling	oai:doaj.org-article:2e1b714265fe4df098176f19f8e89fc22021-12-02T18:50:56ZSprouty2 regulates positioning of retinal progenitors through suppressing the Ras/Raf/MAPK pathway10.1038/s41598-020-70670-22045-2322https://doaj.org/article/2e1b714265fe4df098176f19f8e89fc22020-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-70670-2https://doaj.org/toc/2045-2322Abstract 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.Jian SunJaeho YoonMoonsup LeeYoo-Seok HwangIra O. DaarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jian Sun Jaeho Yoon Moonsup Lee Yoo-Seok Hwang Ira O. Daar Sprouty2 regulates positioning of retinal progenitors through suppressing the Ras/Raf/MAPK pathway
description	Abstract 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.
format	article
author	Jian Sun Jaeho Yoon Moonsup Lee Yoo-Seok Hwang Ira O. Daar
author_facet	Jian Sun Jaeho Yoon Moonsup Lee Yoo-Seok Hwang Ira O. Daar
author_sort	Jian Sun
title	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_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_sort	sprouty2 regulates positioning of retinal progenitors through suppressing the ras/raf/mapk pathway
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/2e1b714265fe4df098176f19f8e89fc2
work_keys_str_mv	AT jiansun sprouty2regulatespositioningofretinalprogenitorsthroughsuppressingtherasrafmapkpathway AT jaehoyoon sprouty2regulatespositioningofretinalprogenitorsthroughsuppressingtherasrafmapkpathway AT moonsuplee sprouty2regulatespositioningofretinalprogenitorsthroughsuppressingtherasrafmapkpathway AT yooseokhwang sprouty2regulatespositioningofretinalprogenitorsthroughsuppressingtherasrafmapkpathway AT iraodaar sprouty2regulatespositioningofretinalprogenitorsthroughsuppressingtherasrafmapkpathway
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Sprouty2 regulates positioning of retinal progenitors through suppressing the Ras/Raf/MAPK pathway

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