Organ Regeneration Based on Developmental Biology

8

telencephalic

neuroepithelium

(Foxg1+)

A

B

apical

apical

Cajal–Retzius cell zones:

Reelin +

CP: Tbr1 +

SVZ: Tbr2 +

VZ: Pax6 +

cortical rosettes cortical layers

(day 10)

mouse SFEBq culture

human SFEBq culture

deep-layer neurons

(Tbr1+/Ctip2+)

upper-layer neurons

(Satb2+/Brn2+)

Cajal-Retzius cells

calretinin+

CSPGs+

MZ

CP

SP

IZ

SVZ

VZ

apical progenitors

(Pax6+/Sox2+)

intermediate progenitors

(Tbr2+)

oRGs (Pax6+/Sox2+)

pia

lumen

(day 42)(day 70)(day 91)

telencephalic

neuroepithelium

(Foxg1+)

cortical

neuroepithelium

(Pax6+/Sox2+)

Fig. 1.3 Self-organizing 3D formation of layered cortical tissues. (a) In mouse ESC culture, the
telencephalic neuroepithelium forms an apical surface inside the SFEBq aggregate. The neuroepi-
thelium transforms into small cortical rosettes, which form multiple layers of neurons and progeni-
tors. (b) In human ESC culture, the apical side of the telencephalic neuroepithelium is located on
the surface of the SFEBq aggregate at an early phase. The neuroepithelium becomes apically
concave in curvature and finally generates a semispherical cortical structure with a lumen inside.
The cortical neuroepithelium self-forms a multilayered structure including MZ (marginal zone),
CP (cortical plate), SP (subplate), IZ (intermediate zone), SVZ (subventricular zone), and VZ (ven-
tricular zone) in the same apical-to-basal order as seen in fetal cortex. Within the CP, the upper-
layer neurons preferentially localize more superficially to deep-layer neurons. Pax6+/Sox2+ oRG
(outer radial glia)-like progenitors that accumulate in the outer portion of the SVZ have a long
basal process extending toward the pia, similar to in vivo oRG

T. Kadoshima et al.