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Dedifferentiation and transdifferentiation: a study of the RPE cell identity.

Barbosa-Sabanero, Karla Y.
http://rave.ohiolink.edu/etdc/view?acc_num=miami1468660645

Abstract Details

2016, Doctor of Philosophy, Miami University, Biological Sciences.
Retinal degenerative diseases eventually lead to blindness affecting millions of people worldwide. To date, there are no effective treatments to cure retinal diseases or strategies to regenerate the damaged retina. For that reason, it is necessary to study cellular signals that trigger retina regeneration in animal models with regeneration potential. This represents an important avenue to pursue. The chick embryo is a suitable model to explore this process because it can regenerate its retina by reprogramming the Retinal Pigmented Epithelium (RPE) by a process called transdifferentiation as long there is an external source of fibroblast growth factor (FGF). In the past, research has been done to study the signals that induce transdifferentiation, however, little is known about the molecular mechanisms that maintain the RPE fate. Previous research from our lab showed that over-expression of Sonic Hedgehog (Shh) inhibits FGF-induced RPE transdifferentiation. This work focusses on the mechanisms by which Gli-1, a downstream effector of Shh signaling, modulates chick retina regeneration. During my dissertation, I worked extensively with chick RPE in vivo and in vitro, studying RPE transdifferentiation, and RPE cell fate maintenance. We used a combinatorial strategy of over-expression and down-regulation studies to dissect the role of Gli-1 in modulating FGF-induced retina regeneration. By performing over-expression studies using RCAS-Gli-1 virus, we show that Gli-1 maintains the RPE fate and RPE markers. Moreover, our knock down studies using morpholinos against Gli-1 showed depigmentation and dedifferentiation of the RPE. This suggests that Gli-1 plays an important role maintaining the identity of the RPE. The results of this research will increase our understanding of the transdifferentiation process and the mechanisms that control RPE cell identity. This knowledge will give insights that could be used to develop effective therapeutic treatments for retinal degenerative diseases.
Katia Del Rio-Tsonis (Advisor)
96 p.
Biology

Recommended Citations

Citations

  • Barbosa-Sabanero, K. Y. (2016). Dedifferentiation and transdifferentiation: a study of the RPE cell identity. [Doctoral dissertation, Miami University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=miami1468660645

    APA Style (7th edition)

  • Barbosa-Sabanero, Karla. Dedifferentiation and transdifferentiation: a study of the RPE cell identity. 2016. Miami University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=miami1468660645.

    MLA Style (8th edition)

  • Barbosa-Sabanero, Karla. "Dedifferentiation and transdifferentiation: a study of the RPE cell identity." Doctoral dissertation, Miami University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=miami1468660645

    Chicago Manual of Style (17th edition)

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© 2016, all rights reserved.
This open access ETD is published by Miami University and OhioLINK.
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