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to activate canonical Wnt pathway in the mammalian intestine (
Kress, Rezza,
Nadjar, Samarut, & Plateroti, 2009
). Further, as mentioned, the adult progen-
itor/stem cells of the
X. laevis
intestine specifically express LGR5 (
Sun et al.,
2010
), a Wnt target (
Moore & Lemischka, 2006; Soubeyran et al., 2001; van
de Wetering et al., 2002
), and P-PTEN and Akt (
Ishizuya-Oka & Shi, 2007
),
both of which are involved in the interplay between Wnt and BMP signals
(
He et al., 2007
). These results strongly suggest the involvement of Wnt sig-
naling pathways in adult stem cell development through interactions with
other signals including BMP (
He et al., 2004
).
Notch signaling pathway is also known to be activated in the adult stem
cells of the adult mammalian intestine (
van Den Brink et al., 2001
) and play a
fundamental role in their maintenance (
Fre et al., 2005; Pellegrinet et al.,
2011
). Considering that Msi1, a positive regulator of Notch pathway by
suppressing translational expression of Numb (
Okano et al., 2005
), is specif-
ically expressed in the adult progenitor/stem cells of the
X. laevis
intestine
(
Ishizuya-Oka et al., 2003
), it is highly possible that Notch signaling path-
way is required to develop and/or maintain the adult stem cells in the am-
phibian intestine. While Paneth cells express Notch ligand Dll4 in the adult
mammalian intestine (
Sato et al., 2011; Vooijs, Liu, & Kopan, 2011
), they
are absent in the amphibian intestine. It raises an intriguing question of what
cells express Notch ligands in this amphibian model. Expression and func-
tional analyses of these Notch- and Wnt-related TH response genes during
amphibian intestinal remodeling await further investigation.
Taken together, one possible scenario at present is that TH upregulates
Shh expression in some larval epithelial cells (precursors of adult stem cells)
and ST3 expression in fibroblasts. Shh then directly acts only on mesenchy-
mal tissues in a paracrine fashion and upregulates the expression of Shh target
genes including Ptc, Smo, Glis, and BMP4. In turn, BMP4 proteins signal
back to the epithelium under the local control of Tolloid/BMP1/Chordin
signaling not only to maintain the adult progenitor/stem cells in an
undifferentiated state but also to promote differentiation of their descen-
dants. However, ST3 causes the basal lamina modification, which in turn
allows contacts between the adult progenitor/stem cells and subepithelial
fibroblasts, leading to the juxtacrine signaling involved in adult epithelial
development. These TH-induced Shh/BMP4 and ST3 signaling pathways
interact withWnt and/or Notch ones and are integrated to establish the stem
cell niche, which enables some of larval epithelial cells to completely dedif-
ferentiate into the adult stem cells that newly generate the intestinal absorp-
tive epithelium (
Fig. 11.5
).
