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Vijay K Kalaskar, James D Lauderdale; Ectopic BMP4 alters Neural Retina and Retinal Pigmented Epithelium Specification. Invest. Ophthalmol. Vis. Sci. 2014;55(13):709.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the role of BMP4 signaling in neural retina and retinal pigmented epithelium (RPE) development by ectopic Bmp4 expression in a mouse whole embryo culture system.
Mouse embryos were obtained from our breeding colony with noon on the day of plug discovery designated as embryonic day 0.5 (E0.5). Wild-type (WT) embryos of CD1-C57BL/6J genetic background were implanted with affi-gel agarose beads treated either with recombinant BMP4 or Noggin proteins in the eye region of embryos at E10.5 and cultured in a standardized serum free medium. Contralateral eyes implanted with BSA protein treated beads were used as control. Eye tissues from these embryos cultured for 10 - 18 hours were analyzed for development and differential gene expression using immunofluorescence, western blot, qRT-PCR and in situ hybridization.
Ectopic expression of Bmp4 in the ocular region altered neural retinal specification and affected the development of RPE pigmentation. The neural retina showed significant down-regulation of specific markers such as Vsx2 (Chx10) and Pax6. While in the RPE, the pigmentation was affected in a stage-dependent manner. When the ocular tissue was exposed to BMP4 before the stage of visible pigmentation (~30-32 somite stage (ss)), the development of pigmentation was inhibited and when exposed after the initiation of pigmentation (~34-35 ss), the RPE showed decreased pigmentation. Further evaluation of the ocular tissue revealed significant changes in the expression of early genes such as Rx, Six3 in the retina and Wnt13, Otx2, Mitf and other downstream pigmentation genes in the RPE in the BMP4 treated eyes compared to the BSA treated eyes.
BMP4 alters the expression of early genes important in neural retinal specification and RPE pigmentation indicating a potential role for BMP4 in RPE and retinal development.
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