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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