| First Author | Rocha-Martins M | Year | 2019 |
| Journal | Development | Volume | 146 |
| Issue | 16 | PubMed ID | 31405994 |
| Mgi Jnum | J:284018 | Mgi Id | MGI:6389941 |
| Doi | 10.1242/dev.176586 | Citation | Rocha-Martins M, et al. (2019) De novo genesis of retinal ganglion cells by targeted expression of Klf4 in vivo. Development 146(16):dev176586 |
| abstractText | 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 Kruppel-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. |
