Her6 and Prox1a are novel regulators of photoreceptor regeneration in the zebrafish retina

Veen, K; Krylov, A; Yu, S; He, J; Boyd, P; Hyde, DR; Mantamadiotis, T; Cheng, LY; Jusuf, PR

Author(s): Veen, K; Krylov, A; Yu, S; He, J; Boyd, P; Hyde, DR; Mantamadiotis, T; Cheng, LY; Jusuf, PR;
Details: Publication Year 2023,Volume 19,Issue #11,Page e1011010
Journal Title: PLoS Genetics
Publication Type: Research article
Abstract: Damage to light-sensing photoreceptors (PRs) occurs in highly prevalent retinal diseases. As humans cannot regenerate new PRs, these diseases often lead to irreversible blindness. Intriguingly, animals, such as the zebrafish, can regenerate PRs efficiently and restore functional vision. Upon injury, mature Muller glia (MG) undergo reprogramming to adopt a stem cell-like state. This process is similar to cellular dedifferentiation, and results in the generation of progenitor cells, which, in turn, proliferate and differentiate to replace lost retinal neurons. In this study, we tested whether factors involved in dedifferentiation of Drosophila CNS are implicated in the regenerative response in the zebrafish retina. We found that hairy-related 6 (her6) negatively regulates of PR production by regulating the rate of cell divisions in the MG-derived progenitors. prospero homeobox 1a (prox1a) is expressed in differentiated PRs and may promote PR differentiation through phase separation. Interestingly, upon Her6 downregulation, Prox1a is precociously upregulated in the PRs, to promote PR differentiation; conversely, loss of Prox1a also induces a downregulation of Her6. Together, we identified two novel candidates of PR regeneration that cross regulate each other; these may be exploited to promote human retinal regeneration and vision recovery.
Keywords: Animals; Animals, Genetically Modified; *Basic Helix-Loop-Helix Transcription Factors/genetics; Cell Differentiation/genetics; Cell Proliferation/genetics; Nerve Regeneration/physiology; Neuroglia; *Retina; *Zebrafish/genetics; *Zebrafish Proteins/genetics; *Homeodomain Proteins/genetics
Department(s): Laboratory Research
PubMed ID: 37930995
Publisher's Version: https://doi.org/10.1371/journal.pgen.1011010
Open Access at Publisher's Site: https://doi.org/10.1371/journal.pgen.1011010
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-01-04 02:56:46

Last Modified: 2024-01-04 02:57:34