@article{ebe93dcae56a44b4aaf2e16317b80954,
title = "Efficient Derivation of Functional Floor Plate Tissue from Human Embryonic Stem Cells",
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.",
author = "Fasano, {Christopher A.} and Chambers, {Stuart M.} and Gabsang Lee and Tomishima, {Mark J.} and Lorenz Studer",
note = "Funding Information: We thank Marysia Plazcek for advice on Floor Plate markers, Doug Epstein for providing the Sonic Enhancers, and Sally Temple for critical reading of the manuscript. We also thank Agnete Kirkeby for providing data on Sonic C25II. C.A.F. is supported by the New York Stem Cell Foundation, S.A.C. is Starr Stem Cell Scholar, M.J.T. is supported in part by the Starr Foundation, and the work is supported in part through grant NS052671 from NINDS/NIH and grant support to L.S. from the Starr Foundation. C.A.F. designed and performed all experiments, interpreted the data, and wrote the manuscript. S.M.C. helped with design and experiments for the microarray study and performed all array analysis. G.L. helped with floor plate functional studies. M.T. was instrumental in the conception of the project and helped with experimental design and data interpretations. L.S. supervised design and execution of the entire study, helped with data interpretations and analysis, and writing of manuscript. ",
year = "2010",
month = apr,
day = "2",
doi = "10.1016/j.stem.2010.03.001",
language = "English (US)",
volume = "6",
pages = "336--347",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "4",
}