There is great excitement in the field of stem cell biology because it may be possible to produce specific kinds of neural cells from ES cells, adult brain stem cells or even bone marrow stem cells. There is a considerable base of knowledge regarding the normal in vivo processes of neural fate induction, stabilization and specification. This important information needs to be expanded in molecular detail so that it can be applied to the goal of obtaining large numbers of stem/progenitor cells that will express only a neural fate when transplanted into damaged or congenitally deficit tissue. The proposed experiments will study the function of several transcription factors that are expressed early in the neural plate and which expand the neural ectoderm when over-expressed. Because these genes are downstream of neural inductive signaling and upstream of neural differentiation genes, we call them neural fate-stabilizing genes. We posit it is important to understand: (1) how neural fate-stabilizing genes function during the earliest steps of neural specification; (2) how these genes interact with each other to expand the embryonic neural stem cell population called the neural plate, and 3) how these genes direct embryonic neural stem cells down the desired differentiation pathways. Once the precise functions of these genes are understood in the embryo, we may be able to regulate their expression to expand neural stem cells, define various stages of neural stem cell specification and put this information to clinical use.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Molecular, Cellular and Developmental Neurosciences 2 (MDCN)
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Horsford, Jonathan
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George Washington University
Anatomy/Cell Biology
Schools of Medicine
United States
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Yan, Bo; Neilson, Karen M; Ranganathan, Ramya et al. (2015) Microarray identification of novel genes downstream of Six1, a critical factor in cranial placode, somite, and kidney development. Dev Dyn 244:181-210
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Yan, Bo; Neilson, Karen M; Moody, Sally A (2009) Notch signaling downstream of foxD5 promotes neural ectodermal transcription factors that inhibit neural differentiation. Dev Dyn 238:1358-65
Schlosser, Gerhard; Awtry, Tammy; Brugmann, Samantha A et al. (2008) Eya1 and Six1 promote neurogenesis in the cranial placodes in a SoxB1-dependent fashion. Dev Biol 320:199-214

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