Organ Regeneration Based on Developmental Biology

: Lef1(+)

: Lmx1a(+), TTR(-)

: Lmx1a(+), TTR(+)

A

B

C D E F

medial pallium

cortical hem

choroid plexus

E12.5

loss of bmpr1a loss of wnt3a

Lmx1a/TTR/DAPI

Foxg1::Venus

The choroid plexus

fails to form.

No morphological sign of hem

and hippocampal development.

Lmx1a(+)/TTR(+)

Lmx1a(+)/TTR(-)

Foxg 1 (+)/Lef1(+)/Lhx 2 (+)

: KA1(+)

: Zbtb20(+)

: Prox1(+)

: Zbtb20(+)

CA3 type neuron

DG type neuron

E15.5-

Fig. 1.6 Induction of dorsomedial telencephalon. (a) Schematic of the segmental development of
the dorsomedial telencephalon. There are three distinct regions: the choroid plexus, cortical hem,
and medial pallium. During the embryonic phase, Prox1+ hippocampal dentate granule neurons
are first induced in the dorsomedial edge of medial pallium (E12.5-) and migrate along a curved
trajectory (E12.5–15.5). Then the cell fate of CA neurons is determined (CA3 (KA1+): E14.5- and
CA1 (SCID+): E15.5-) with migration like that of DG neurons, resulting in the formation of a typi-
cal hippocampal structure. Disrupting the BMP signaling caused lack of choroid plexus tissues,
whereas reduction of Wnt 3a in cortical hem severely affected the formation of hippocampal struc-
ture. (b) Schematic of the induction method for dorsomedial telencephalic tissues. (c) Bright-field
view of one aggregate cultured using choroid plexus induction method on day 42. (d)
Immunohistochemistry of choroid plexus tissues derived from hESCs. The pleated epithelia are
positive for Lmx1a and TTR. TTR mainly stained apically. (e) Schematic of hESC-derived dorso-
medial telencephalic tissues. Choroid plexus, hem, and medial pallium regions are continuously
generated as seen in  vivo. (f) Schematic of hESC-derived hippocampal neurons. KA1-positive
neurons (CA type) tended to have large cell bodies; in contrast, Prox1-positive neurons (DG type)
mostly had small somata. Scale bars: 500 μm in C and 200 μm in D