Open AccessEmbryonic stem cells neural differentiation qualifies the role of Wnt/β‐Catenin signals in human telencephalic specification and regionalization
Author(s) -
Nicoleau Camille,
Varela Christine,
Bonnefond Caroline,
Maury Yves,
Bugi Aurore,
Aubry Laetitia,
Viegas Pedro,
BourgoisRocha Fany,
Peschanski Marc,
Perrier Anselme L
Publication year - 2013
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1462
Subject(s) - biology , ganglionic eminence , wnt signaling pathway , induced pluripotent stem cell , neuroscience , embryonic stem cell , sonic hedgehog , neural stem cell , neurogenesis , neural development , progenitor cell , cerebrum , directed differentiation , neural plate , microbiology and biotechnology , stem cell , signal transduction , central nervous system , embryogenesis , genetics , embryo , gene
Wnt‐ligands are among key morphogens that mediate patterning of the anterior territories of the developing brain in mammals. We qualified the role of Wnt‐signals in regional specification and subregional organization of the human telencephalon using human pluripotent stem cells (hPSCs). One step neural conversion of hPSCs using SMAD inhibitors leads to progenitors with a default rostral identity. It provides an ideal biological substrate for investigating the role of Wnt signaling in both anteroposterior and dorso‐ventral processes. Challenging hPSC‐neural derivatives with Wnt‐antagonists, alone or combined with sonic hedgehog (Shh), we found that Wnt‐inhibition promote both telencephalic specification and ventral patterning of telencephalic neural precursors in a dose‐dependent manner. Using optimal Wnt‐antagonist and Shh‐agonist signals we produced human ventral‐telencephalic precursors, committed to differentiation into striatal projection neurons both in vitro and in vivo after homotypic transplantation in quinolinate‐lesioned rats. This study indicates that sequentially organized Wnt‐signals play a key role in the development of human ventral telencephalic territories from which the striatum arise. In addition, the optimized production of hPSC‐derived striatal cells described here offers a relevant biological resource for exploring and curing Huntington disease. S tem C ells 2013;31:1763‐1774