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Sci Rep 2020 Aug 13;101:13752. doi: 10.1038/s41598-020-70670-2.
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Sprouty2 regulates positioning of retinal progenitors through suppressing the Ras/Raf/MAPK pathway.

Sun J , Yoon J , Lee M , Hwang YS , Daar IO .

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.

PubMed ID: 32792568
PMC ID: PMC7426826
Article link: Sci Rep
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: dvl2 efnb1 fgfr2 hras mapk1 pax6 prkcd raf1 rax spry1 spry2 spry4
GO keywords: eye development
Antibodies: Casp3 Ab1 GFP Ab16 H3f3a Ab9
Morpholinos: dvl2 MO1 efnb1 MO1 prkcd MO2 spry2 MO3

Disease Ontology terms: microphthalmia
Phenotypes: Xla Wt + dvl2 MO (Fig. 2 A r2 c1) [+]

Article Images: [+] show captions
References [+] :
Basson, Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction. 2005, Pubmed, Xenbase