Pax6 Is a Human Neuroectoderm Cell Fate Determinant

Cell Stem Cell, Volume 7, Issue 1, 90-100, 2 July 2010 | Copyright © 2010 Elsevier Inc. All rights reserved. | 10.1016/j.stem.2010.04.017
Pax6 Is a Human Neuroectoderm Cell Fate Determinant
Xiaoqing Zhang, Cindy T. Huang, Jing Chen, Matthew T. Pankratz, Jiajie Xi, Jin Li, Ying Yang, Timothy M. LaVaute, Xue-Jun Li, Melvin Ayala, Gennadiy I. Bondarenko, Zhong-Wei Du, Ying Jin, Thaddeus G. Golos, Su-Chun Zhang

Highlights
Pax6 is ubiquitously expressed in the human neural plate
Pax6 is necessary and sufficient for human neuroectoderm (NE) specification
Pax6 represses pluripotent genes and activates neural genes
Mouse NE specification does not require Pax6

Summary
The transcriptional regulation of neuroectoderm (NE) specification is unknown. Here we show that Pax6 is uniformly expressed in early NE cells of human fetuses and those differentiated from human embryonic stem cells (hESCs). This is in contrast to the later expression of Pax6 in restricted mouse brain regions. Knockdown of Pax6 blocks NE specification from hESCs. Overexpression of either Pax6a or Pax6b, but not Pax6▵PD, triggers hESC differentiation. However, only Pax6a converts hESCs to NE. In contrast, neither loss nor gain of function of Pax6 affects mouse NE specification. Both Pax6a and Pax6b bind to pluripotent gene promoters but only Pax6a binds to NE genes during human NE specification. These findings indicate that Pax6 is a transcriptional determinant of the human NE and suggest that Pax6a and Pax6b coordinate with each other in determining the transition from pluripotency to the NE fate in human by differentially targeting pluripotent and NE genes.

open here please:
http://www.cell.com/cell-stem-cell/abstract/S1934-5909(10)00172-4

full-text:
http://download.cell.com/cell-stem-cell/pdf/PIIS1934590910001724.pdf?intermediate=true