Organ Regeneration Based on Developmental Biology

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9.5.4 Mechanism of A-P Axis Formation Along the Body

Trunk Elongation

During embryogenesis, formation of the rostral body trunk (the head and the
anterior- most trunk region) occurs by the end of gastrulation (~E8.5), while elonga-
tion of the caudal body trunk continues in later embryogenesis (E8.5–E13.5)
(Wilson et al. 2009 ). This axis elongation is attributed to the continuous supply of
cells at the caudal end of the embryo, the so-called tail bud mesenchyme, which is
marked by expression of T and Cdx2 (Figs. 9.5 and 9.6).
The caudal immature population is maintained by Wnt and FGF signals and the
suppression of retinoic acid signals by the degradation enzyme Cyp26s (cytochrome
P450, family 26). Wnt directly promotes T expression, and T upregulates the expres-
sion of Wnt3a in a positive-feedback manner. Indeed, both T and Wnt3a knockout

Posterior

Intermediate

Mesoderm

(metanephric precursor)

E8.5 E9.5 E10.5

Osr1+Wt1+

Pax2+

Six2+

Gdnf+

Hox11+

Osr1+

Hox11+Wt1+

E3.5

Epiblast

E6.5

Blastocyst

Posterior

Nascent

Mesoderm

(Axial progenitor)

IntermediatMiddlee

Mesoderm

(mesonephric

nephron

progenitor)

Osr1+Wt1+

Pax2+

Six2+

Gdnf+

Hox11-

T+

Cdx2+

Tbx6+

Oct3/4+Nanog+ Fgf5+ Osr1+

Wt1+

Pax2+

Six2+

Gdnf+

Hox11-

Anterior

IntermediateMesoderm

(pronephric

anlagen)

Wolffian Duct

extend

caudally

primive

streak

T+

Ureteric Bud

E7.5

Osr1+Pax2+

Lim1+

Osr1-

Pax2+Lim1+

caudallystay

Metanephric

Mesenchyme

(metanephric

nephron

progenitor)

Mesonephros

Tail

PosterioNascentr

Mesoderm

(Axial progenitor)

T+

Cdx2+

Tbx6+

stay

caudally

Fig. 9.5 Schematic of early kidney lineage specification. The transition timing from the T-positive
immature population to the T-negative differentiated population determines the anteroposterior
level in the body trunk

9 Early Kidney Specification and Its Recapitulation by Pluripotent Stem Cells