11ESC-derived oRG-like cells tended to be horizontal, as observed in oRG cells
in vivo (Fietz et al. 2010 ; Hansen et al. 2010 ). These data indicate that human ESC-
derived cortical tissues recapitulate oRG characteristics, such as similar timing in
their appearance and similar molecular marker expression, cellular morphology,
and location. Therefore, 3D cortical tissue generated from human PSCs will be a
useful tool in studying these species-specific progenitors, which likely play a sig-
nificant role in cortical evolution.
1.3 Ventralizing Telencephalic Tissues
1.3.1 Development of the Ventral Telencephalon In Vivo
The ventral telencephalon (subpallium) is subdivided into the lateral ganglionic
eminence (LGE), medial ganglionic eminence (MGE), caudal ganglionic eminence
(CGE), the septum, and the ventral-most telencephalic stalk regions (e.g., the pre-
optic and anterior entopeduncular areas) (Sousa and Fishell 2010 ). The LGE is the
origin of striatal projection neurons (Marı́n et al. 2000 ), whereas MGE and CGE
appear to be the primary source of cortical and striatal GABAergic interneurons
(Anderson et al. 1997 , Nóbrega-Pereira et al. 2010 ). Previous studies have demon-
strated the importance of patterning signaling via sonic hedgehog (Shh) in subpal-
lial development (Shimamura et al. 1995 ; Echelard et al. 1993 ; Fuccillo et al. 2004 ,
2006 ), and the signals trigger cascades that lead to generation of cortical interneu-
rons by inducing key transcription factors, such as Gsh2 in LGE, Nkx2.1 in MGE,
and CoupTFII in CGE (Butt et al. 2008 ; Fuccillo et al. 2006 ; Corbin et al. 2003 ;
Wonders and Anderson 2006 ). In the mouse embryo, Shh is first observed at an
early developmental phase (E8–E9.5) in the diencephalon and mesendoderm, adja-
cent to the ventral telencephalon. This Shh expression induces Nkx2.1 in the MGE
area (Sousa and Fishell 2010 ). Then Shh is expressed by the MGE and preoptic area
by E12.5, and Gsh2 is expressed between the Nkx2.1 and Pax6 domains. The Gsh2+/
Nkx2.1− domain possesses LGE identity (Flandin et al. 2010 ; Waclaw et al. 2009 )
(Fig. 1.5a).
There are temporal time windows in the development of ventral telencephalon.
Removal of Shh responsiveness from the ventral telencephalon by conditional dele-
tion of smoothened by E9.5 results in strong abnormalities of patterning, whereas
removal by E12.5 causes only minor patterning abnormalities (Dessaud et al. 2007 ).
In humans, some studies report that most cortical interneurons undergo their termi-
nal mitosis in the cortical subventricular zone (Letinic et al. 2002 ), yet recent stud-
ies show that cortical interneurons are actually generated from subpallium and then
tangentially migrate into the cortical layer. This suggests a preserved developmental
patterning of ventral telencephalon for generating GABAergic interneurons, as in
mice (Anderson et al. 1997 ; Ma et al. 2013 ; Hansen et al. 2013 ).
1 Telencephalic Tissue Formation in 3D Stem Cell Culture