Activin/Nodal Signaling Supports Retinal Progenitor Specification in a Narrow Time Window during Pluripotent Stem Cell Neuralization

Bertacchi, Michele; Lupo, Giuseppe; Pandolfini, Luca; Casarosa, Simona; D’Onofrio, Mara; Pedersen, Roger&nbsp;a; Harris, William&nbsp;a; Cremisi, Federico

doi:10.1016/j.stemcr.2015.08.011

Retinal progenitors are initially found in the anterior neural plate region known as the eye field, whereas neighboring areas undertake telencephalic or hypothalamic development. Eye field cells become specified by switching on a network of eye field transcription factors, but the extracellular cues activating this network remain unclear. In this study, we used chemically defined media to induce in vitro differentiation of mouse embryonic stem cells (ESCs) toward eye field fates. Inhibition of Wnt/β-catenin signaling was sufficient to drive ESCs to telencephalic, but not retinal, fates. Instead, retinal progenitors could be generated from competent differentiating mouse ESCs by activation of Activin/Nodal signaling within a narrow temporal window corresponding to the emergence of primitive anterior neural progenitors. Activin also promoted eye field gene expression in differentiating human ESCs. Our results reveal insights into the mechanisms of eye field specification and open new avenues toward the generation of retinal progenitors for translational medicine.

Titolo:	Activin/Nodal Signaling Supports Retinal Progenitor Specification in a Narrow Time Window during Pluripotent Stem Cell Neuralization
Autori:	BERTACCHI, MICHELE Lupo, Giuseppe PANDOLFINI, LUCA Casarosa, Simona D’Onofrio, Mara Pedersen, Roger a Harris, William a CREMISI, Federico mostra contributor esterni nascondi contributor esterni
Data di pubblicazione:	2015
Rivista:	STEM CELL REPORTS
Digital Object Identifier (DOI):	http://dx.doi.org/10.1016/j.stemcr.2015.08.011
Parole Chiave:	Activins; Animals; Cell Differentiation; Cell Line; Embryonic Stem Cells; Gene Expression Regulation, Developmental; Humans; Mice; Neural Stem Cells; Nodal Protein; Pluripotent Stem Cells; Retina; Wnt Signaling Pathway; Signal Transduction
Handle:	http://hdl.handle.net/11384/59761
Appare nelle tipologie:	1.1 Articolo in rivista

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