Organ Regeneration Based on Developmental Biology

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mice exhibit caudal truncation of the embryo (Takada et al. 1994 ; Yamaguchi et al.
1999 ). Contrastingly, cells undergo differentiation by leaving the tail bud region and
migrating to the former side, where they receive less Wnt/FGF signal and more reti-
noic acid signal. Such continuous recruitment of differentiated cells enables forma-
tion of the caudal body trunk, including somite formation. Therefore, the timing of
exposure to differentiation signals determines the axial level within the caudal body
trunk (Aulehla and Pourquie 2010 ) (Figs. 9.5 and 9.6).
Because the caudal body trunk includes both neural and mesodermal tissues, it is
regarded as a bipotent progenitor, namely, the “axial progenitor” or “neuromesoder-
mal progenitor.” Recent in  vivo studies have provided supporting evidence using
genetic lineage tracing and genetic manipulation studies (Tzouanacou et al. 2009 ;
Takemoto et al. 2011 ). These bipotent cells have been recently classified as a T and
Sox2 double-positive cell population (Henrique et al. 2015 ). However, the distinct
origin of this bipotent population in the early gastrulation-stage embryo (E6.5–
E7.5) is not known, and the contribution of this population to the metanephros is
unclear.

E8.5 E9.5 E10.5

Tail bud mesenchyme
(= posterior nascent mesoderm)

Head region

Anterior IM Forelimb

level

Posterior IM

Caudally elongating

Wolffian duct

Metanephric

mesenchyme

mesonephros

tail

tail

head

RA

Wnt/Fgf

hyme

esoderm)

Head region

Forelimb

level

PosteriorIM

Caudallyelongating

Wolffffianduct

Metanephric

mesenchyme

mesonephros

tail

tail

RA

Wnt/FgWWt/Fgff

RA

Wnt/Fgf

Ureteric bud

Head region

Hindlimb

level

Middle IM

Fig. 9.6 Schematic of the body trunk elongation process during development. The T-positive tail
bud mesenchyme persists in the caudal end of the embryo up to E13.5, leading to development of
the caudal body trunk. The caudal immature cell population is maintained in a Wnt/Fgf-rich envi-
ronment, whereas retinoic acid signaling promotes differentiation. Green, intermediate mesoderm;
blue, Wolffian duct; orange, caudal immature population

A. Taguchi and R. Nishinakamura