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remaining cortical domain can express Lef1 and Lhx2, which results in dorsomedial
pattern formation as seen in vivo (days 21–42). Our technology now gives researchers
new means to investigate hippocampal biology, disease, and potential therapies.
1.5 Closing Remarks and Future Perspective
Here we have reviewed recent advances in 3D organogenesis with regard to telen-
cephalic tissue induction. Generation of 3D tissue will allow the morphogenesis as
seen in human development in vivo. The human PSC-derived cortical tissues in 3D
culture are thought to have a very similar transcriptional profile to human fetal cor-
tex (Mariani et al. 2012 ; Camp et al. 2015 ). These studies reveal that human PSC-
derived 3D human cortical tissues recapitulate not only the cortical architecture and
cellular behavior but also genetic features. Therefore human PSC-derived cortical
tissues can be a powerful tool for understanding human corticogenesis and for neu-
rodevelopmental disease modeling. Indeed, the cortical tissues derived from PSCs
from a patient with microcephaly showed premature neuronal differentiation
(Lancaster et al. 2013 ). However, to generate fully functional cortical tissues
in vitro, we have to overcome some technical limitations. In particular, an insuffi-
cient supply of oxygen and nutrients is a critical problem for long-term culture.
Vascular network formation in the in vitro human cortical tissues could be one of
the promising solutions. In the mouse fetal cortex, vascularization starts around
E12.5, and it supplies nutrients and provides niches for neural stem/progenitor cells
(Stubbs et al. 2009 ). A recent study showed the generation of vascularized liver
from human PSCs in 3D culture (Takebe et al. 2013 ), and this method is also appli-
cable to brain tissues (Takebe et al. 2015 ). Such attempts would allow better reca-
pitulation of human corticogenesis in vitro. Moreover, induction of more complex
telencephalic tissues will open the next generation of tissue formation and medical
applications with regard to the complex functions of the human brain. Generation of
a broad area of telencephalon including pallium–subpallium or neo- to- archi cortical
tissue in sequential order may allow the induction of more complex tissue such as
amygdala, hippocampus, or claustrum in vitro. If so, this would enable a deeper
exploration of higher brain functions such as the formation of episodic memory,
personality, intention, or emotion.
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