Generation of Functional Eyes from Pluripotent Cells

Abstract

The directed differentiation of pluripotent cells into specific cell-types is a major hurdle in regenerative medicine. This study shows the eye field transcription factor factors can direct pluripotent cells into functioning frog eyes.

Noggin 1 overexpression in retinal progenitors affects bipolar cell generation

“…The overexpression of high levels of noggin 1 activates Nodal/TGFb and Shh pathways in ACES cells eliciting a retinal fate in vitro, and these cells are able to induce the formation of a normal eye after transplantation in the eye field region (Lan et al, 2009;Messina et al, 2015). Similar results were obtained treating ACES cells with Noggin protein (Viczian et al, 2009). Moreover, noggin shows a conserved expression in the adult retina of different vertebrates (Messina et al, 2014).…”

“…Previous studies have analysed noggin 1 role starting from the initial phases of Xenopus development (Smith and Harland, 1992;Bayramov et al, 2011) or in ex-vivo experiments using animal cap explants (Zuber et al, 2003;Lan et al, 2009;Viczian et al;2009;Wong et al, 2015;Messina et al, 2015). No data are reported for a possible role of noggin 1 in later stages of eye development in vivo, however.…”

“…Elegant studies suggested that BMP inhibition by noggin overexpression could confer a retina-forming competence to Xenopus animal blastomeres normally not fated to become retina (Moore and Moody, 1999). In the last ten years, noggin 1 was also shown to contribute to the activation of EFTFs in Xenopus laevis pluripotent animal cap embryonic stem (ACES) cells (Zuber et al, 2003;Lan et al, 2009;Viczian et al, 2009). The overexpression of high levels of noggin 1 activates Nodal/TGFb and Shh pathways in ACES cells eliciting a retinal fate in vitro, and these cells are able to induce the formation of a normal eye after transplantation in the eye field region (Lan et al, 2009;Messina et al, 2015).…”

Modeling autosomal dominant optic atrophy using induced pluripotent stem cells and identifying potential therapeutic targets

“…In Xenopus, Noggintreated pluripotent cells were found to be able to differentiate into a multipotent retinal progenitor lineage, which facilitated functional eye formation following transplantation in vivo [26]. colleagues also reported that a high-dose treatment of Noggin promoted retinal cell differentiation in Xenopus embryonic stem cells [27].…”

La révolution 3D des cellules souches : fabrication d’une rétinein vitro

“…Bien que ces travaux montrent qu'il est possible d'induire in vitro des neurones de rétine, les conditions n'étaient pas réunies pour forcer ces cellules à s'organiser en une structure épithéliale. En revanche, des progéniteurs rétiniens issus de la différen-ciation de CSE puis réimplantés dans un embryon de grenouille, sur ses flancs par exemple, s'agencent spontanément pour former des rétines ectopiques [6]. Une étape était franchie, mais d'autres défis restaient à relever pour réaliser le rêve de certains de former de toute pièce un oeil ex vivo.…”