Format

Send to

Choose Destination
Development. 2019 Aug 21;146(16). pii: dev176586. doi: 10.1242/dev.176586.

De novo genesis of retinal ganglion cells by targeted expression of Klf4 in vivo.

Author information

1
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil silveira@biof.ufrj.br rocha@mpi-cbg.de.
2
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
3
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil.
4
Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil.

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.This article has an associated 'The people behind the papers' interview.

KEYWORDS:

Cell fate; Cell potency; In vivo reprogramming; RGC; Regeneration

PMID:
31405994
DOI:
10.1242/dev.176586

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center