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let-7 MicroRNA-Mediated Regulation of Shh Signaling and the Gene Regulatory Network Is Essential for Retina Regeneration
Upon injury, Müller glia cells of the zebrafish retina reprogram themselves to progenitor cells with stem cell characteristics. This necessity for retina regeneration is often compromised in mammals. We explored the significance of developmentally inevitable Sonic hedgehog signaling and found its ne...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946716/ https://www.ncbi.nlm.nih.gov/pubmed/29719254 http://dx.doi.org/10.1016/j.celrep.2018.04.002 |
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author | Kaur, Simran Gupta, Shivangi Chaudhary, Mansi Khursheed, Mohammad Anwar Mitra, Soumitra Kurup, Akshai Janardhana Ramachandran, Rajesh |
author_facet | Kaur, Simran Gupta, Shivangi Chaudhary, Mansi Khursheed, Mohammad Anwar Mitra, Soumitra Kurup, Akshai Janardhana Ramachandran, Rajesh |
author_sort | Kaur, Simran |
collection | PubMed |
description | Upon injury, Müller glia cells of the zebrafish retina reprogram themselves to progenitor cells with stem cell characteristics. This necessity for retina regeneration is often compromised in mammals. We explored the significance of developmentally inevitable Sonic hedgehog signaling and found its necessity in MG reprogramming during retina regeneration. We report on stringent translational regulation of sonic hedgehog, smoothened, and patched1 by let-7 microRNA, which is regulated by Lin28a, in Müller glia (MG)-derived progenitor cells (MGPCs). We also show Shh-signaling-mediated induction of Ascl1 in mouse and zebrafish retina. Moreover, Shh-signaling-dependent regulation of matrix metalloproteinase9, in turn, regulates Shha levels and genes essential for retina regeneration, such as lin28a, zic2b, and foxn4. These observations were further confirmed through whole-retina RNA-sequencing (RNA-seq) analysis. This mechanistic gene expression network could lead to a better understanding of retina regeneration and, consequently, aid in designing strategies for therapeutic intervention in human retinal diseases. |
format | Online Article Text |
id | pubmed-5946716 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-59467162018-05-14 let-7 MicroRNA-Mediated Regulation of Shh Signaling and the Gene Regulatory Network Is Essential for Retina Regeneration Kaur, Simran Gupta, Shivangi Chaudhary, Mansi Khursheed, Mohammad Anwar Mitra, Soumitra Kurup, Akshai Janardhana Ramachandran, Rajesh Cell Rep Article Upon injury, Müller glia cells of the zebrafish retina reprogram themselves to progenitor cells with stem cell characteristics. This necessity for retina regeneration is often compromised in mammals. We explored the significance of developmentally inevitable Sonic hedgehog signaling and found its necessity in MG reprogramming during retina regeneration. We report on stringent translational regulation of sonic hedgehog, smoothened, and patched1 by let-7 microRNA, which is regulated by Lin28a, in Müller glia (MG)-derived progenitor cells (MGPCs). We also show Shh-signaling-mediated induction of Ascl1 in mouse and zebrafish retina. Moreover, Shh-signaling-dependent regulation of matrix metalloproteinase9, in turn, regulates Shha levels and genes essential for retina regeneration, such as lin28a, zic2b, and foxn4. These observations were further confirmed through whole-retina RNA-sequencing (RNA-seq) analysis. This mechanistic gene expression network could lead to a better understanding of retina regeneration and, consequently, aid in designing strategies for therapeutic intervention in human retinal diseases. Cell Press 2018-05-02 /pmc/articles/PMC5946716/ /pubmed/29719254 http://dx.doi.org/10.1016/j.celrep.2018.04.002 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kaur, Simran Gupta, Shivangi Chaudhary, Mansi Khursheed, Mohammad Anwar Mitra, Soumitra Kurup, Akshai Janardhana Ramachandran, Rajesh let-7 MicroRNA-Mediated Regulation of Shh Signaling and the Gene Regulatory Network Is Essential for Retina Regeneration |
title | let-7 MicroRNA-Mediated Regulation of Shh Signaling and the Gene Regulatory Network Is Essential for Retina Regeneration |
title_full | let-7 MicroRNA-Mediated Regulation of Shh Signaling and the Gene Regulatory Network Is Essential for Retina Regeneration |
title_fullStr | let-7 MicroRNA-Mediated Regulation of Shh Signaling and the Gene Regulatory Network Is Essential for Retina Regeneration |
title_full_unstemmed | let-7 MicroRNA-Mediated Regulation of Shh Signaling and the Gene Regulatory Network Is Essential for Retina Regeneration |
title_short | let-7 MicroRNA-Mediated Regulation of Shh Signaling and the Gene Regulatory Network Is Essential for Retina Regeneration |
title_sort | let-7 microrna-mediated regulation of shh signaling and the gene regulatory network is essential for retina regeneration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946716/ https://www.ncbi.nlm.nih.gov/pubmed/29719254 http://dx.doi.org/10.1016/j.celrep.2018.04.002 |
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