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Neural Induction and Patterning in Mammalian Pluripotent Stem Cells

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Embryonic stem (ES) cells are derived from the inner cell mass (ICM) of blastocyst stage embryos, while induced pluripotent stem (iPS) cells are generated from somatic cells through transient overexpression of defined transcription factors. When transplanted into a preimplantation embryo, ES cells and iPS cells can differentiate into any cell type, including germ cells. Moreover, they can grow in culture indefinitely while maintaining pluripotency. In vitro differentiation of ES cells and iPS cells recapitulates many aspects of in vivo embryogenesis. The acquisition of neural fates (neural induction) in ES cells can be controlled by bone morphogenetic protein (BMP), fibroblast growth factor (FGF), and Wnt signaling, while the production of specific neural cell types (neural patterning) can be controlled by exogenous patterning signals such as Wnt, BMP, Shh, FGF, and retinoic acid. In response to these signals, ES cells can differentiate into a wide range of neural cell types that correlate with their positions along the anterior-posterior and dorsal-ventral axes. ES cell and iPS cell culture systems will provide materials for cell replacement therapy, and can be used as in vitro models for disease and drug testing as well as development. Here we review spatiotemporal control of neural differentiation of mammalian pluripotent stem cells, with a special emphasis on the relationship between in vivo embryogenesis and in vitro ES cell differentiation. Retinal differentiation from ES cells and iPS cells is also outlined.

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Keywords: Cell fate; bone morphogenetic protein; default model; embryogenesis; embryonic stem (ES) cell; fibroblast growth factor; induced pluripotent stem (iPS) cell; neurogenesis; photoreceptor; regeneration; retina; retinal pigment epithelium; stromal cell-derived inducing activity; xenopus laevis

Document Type: Research Article

Publication date: 01 June 2011

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  • CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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