Efficient derivation of functional floor plate tissue from human embryonic stem cells.

Cell Stem Cell

Developmental Biology Program, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USA; Department of Neurosurgery, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USA. Electronic address:

Published: April 2010

AI Article Synopsis

  • The floor plate (FP) is essential for neural development and is located at the embryo's ventral midline, but research on human FP development has been limited.
  • Researchers successfully derived human embryonic stem cell (hESC)-derived FP tissue that can secrete crucial molecules like Netrin-1 and SHH, vital for tissue patterning.
  • The study reveals that FP induction relies on early exposure to SHH, which inhibits the Dkk-1 gene, ultimately leading to the formation of FP over anterior neurectoderm (AN) and influences regional identity in the derived FP.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336800PMC
http://dx.doi.org/10.1016/j.stem.2010.03.001DOI Listing

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