Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1

Some adult-onset disorders may be linked to dysregulated embryonic development, yet the mechanisms underlying this association remain poorly understood. Congenital retinal degenerative diseases are blinding disorders characterized by postnatal degeneration of photoreceptors, and affect nearly 2 mill...

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Bibliographic Details
Published in:Scientific reports Vol. 6; no. 1; p. 33887
Main Authors: Yan, Naihong, Cheng, Lin, Cho, Kinsang, Malik, Muhammad Taimur A., Xiao, Lirong, Guo, Chenying, Yu, Honghua, Zhu, Ruilin, Rao, Rajesh C., Chen, Dong Feng
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 28.09.2016
Nature Publishing Group
Subjects:
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Degenerative diseases
Derepression
Embryogenesis
Embryonic growth stage
Fetuses
Gene deletion
Histone methyltransferase
Homeostasis
Humanities and Social Sciences
multidisciplinary
Photoreceptors
Retina
Retinal degeneration
Science
Science (multidisciplinary)
ISSN:2045-2322, 2045-2322
Online Access:Get full text
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Summary:Some adult-onset disorders may be linked to dysregulated embryonic development, yet the mechanisms underlying this association remain poorly understood. Congenital retinal degenerative diseases are blinding disorders characterized by postnatal degeneration of photoreceptors, and affect nearly 2 million individuals worldwide, but ∼50% do not have a known mutation, implicating contributions of epigenetic factors. We found that embryonic deletion of the histone methyltransferase (HMT) Ezh2 from all retinal progenitors resulted in progressive photoreceptor degeneration throughout postnatal life, via derepression of fetal expression of Six1 and its targets. Forced expression of Six1 in the postnatal retina was sufficient to induce photoreceptor degeneration. Ezh2 , although enriched in the embryonic retina, was not present in the mature retina; these data reveal an Ezh2 -mediated feed-forward pathway that is required for maintaining photoreceptor homeostasis in the adult and suggest novel targets for retinal degeneration therapy.
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ISSN:2045-2322
2045-2322
DOI:10.1038/srep33887