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      Efficient Derivation of Functional Floor Plate Tissue from Human Embryonic Stem Cells

      , , , ,
      Cell Stem Cell
      Elsevier BV

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          Abstract

          The floor plate (FP) is a critical signaling center during neural development located along the ventral midline of the embryo. Little is known about human FP development because of the lack of tissue accessibility. Here we report the efficient derivation of human embryonic stem cell (hESC)-derived FP tissue capable of secreting Netrin-1 and SHH and patterning primary and hESC derived tissues. FP induction in hESCs is dependent on early SHH exposure and occurs at the expense of anterior neurectoderm (AN). Global gene expression and functional studies identify SHH-mediated inhibition of Dkk-1 as key factor in FP versus AN specification. hESC-derived FP tissue is shown to be of anterior SIX6+ character but is responsive to caudalizing factors suppressing SIX6 expression and inducing a shift in usage of region-specific SHH enhancers. These data define the early signals that drive human FP versus AN specification and determine regional identity in hESC-derived FP. Copyright c) 2010 Elsevier Inc. All rights reserved.

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          Author and article information

          Journal
          Cell Stem Cell
          Cell Stem Cell
          Elsevier BV
          19345909
          April 2010
          April 2010
          : 6
          : 4
          : 336-347
          Article
          10.1016/j.stem.2010.03.001
          4336800
          20362538
          22a13225-4797-436d-8dcf-dd39c2a5a77d
          © 2010

          https://www.elsevier.com/tdm/userlicense/1.0/

          https://www.elsevier.com/open-access/userlicense/1.0/


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