PUBLICATION
De novo genesis of retinal ganglion cells by targeted expression of Klf4 in vivo
- Authors
- Rocha-Martins, M., de Toledo, B.C., Santos-França, P.L., Oliveira-Valença, V.M., Vieira-Vieira, C.H., Matos-Rodrigues, G.E., Linden, R., Norden, C., Martins, R.A.P., Silveira, M.S.
- ID
- ZDB-PUB-190814-10
- Date
- 2019
- Source
- Development (Cambridge, England) 146(16): (Journal)
- Registered Authors
- Norden, Caren
- Keywords
- Cell fate, Cell potency, In vivo reprogramming, RGC, Regeneration
- MeSH Terms
-
- Animals
- Cell Cycle
- Female
- Homeodomain Proteins/metabolism
- Kruppel-Like Transcription Factors/genetics
- Kruppel-Like Transcription Factors/physiology*
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Nerve Regeneration
- Neural Stem Cells/physiology
- Neurogenesis*
- Rats
- Retinal Ganglion Cells/physiology*
- Transcription Factor Brn-3A/metabolism
- Transcription Factor Brn-3B/metabolism
- Zebrafish
- Zebrafish Proteins/physiology
- PubMed
- 31405994 Full text @ Development
Citation
Rocha-Martins, M., de Toledo, B.C., Santos-França, P.L., Oliveira-Valença, V.M., Vieira-Vieira, C.H., Matos-Rodrigues, G.E., Linden, R., Norden, C., Martins, R.A.P., Silveira, M.S. (2019) De novo genesis of retinal ganglion cells by targeted expression of Klf4 in vivo. Development (Cambridge, England). 146(16):.
Abstract
Retinal ganglion cell (RGC) degeneration is a hallmark of glaucoma, the most prevalent cause of irreversible blindness. Thus, therapeutic strategies are needed to protect and replace these projection neurons. One innovative approach is to promote de novo genesis of RGCs via manipulation of endogenous cell sources. Here, we demonstrate that the pluripotency regulator gene Krüppel-like factor 4 (Klf4) is sufficient to change the potency of lineage-restricted retinal progenitor cells to generate RGCs in vivo Transcriptome analysis disclosed that the overexpression of Klf4 induces crucial regulators of RGC competence and specification, including Atoh7 and Eya2 In contrast, loss-of-function studies in mice and zebrafish demonstrated that Klf4 is not essential for generation or differentiation of RGCs during retinogenesis. Nevertheless, induced RGCs (iRGCs) generated upon Klf4 overexpression migrate to the proper layer and project axons aligned with endogenous fascicles that reach the optic nerve head. Notably, iRGCs survive for up to 30 days after in vivo generation. We identified Klf4 as a promising candidate for reprogramming retinal cells and regenerating RGCs in the retina.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping