Biology Reference
In-Depth Information
Shh (+)
LGR5 (+)
Msi1 (+)
Akt (+)
IFABP (-)
PY (++)
Shh (-)
IFABP (+)
PY (+)
Shh (-)
IFABP (+)
PY (+)
Shh (+)
IFABP (-)
PY (++)
Adult epithelium
Larval epithelium
(except for stem cell)
(Proliferation
and
differentiation)
Stem cell
(Dedifferentiation)
(1)
(1) + (2)
(2)
BL
BL
BL
TH
Figure 11.4 Schematic model showing adult stem cell development during amphibian
intestinal remodeling. Cells that have a potency to dedifferentiate into adult stem cells
reside in the larval epithelium before metamorphosis. By the direct action of thyroid
hormone (TH), these cells partly dedifferentiate and begin to express Shh (1; intracellular
pathway). However, they require TH signaling in nonepithelial tissues (2; extracellular
pathway) to fully dedifferentiate into adult stem cells that express all of the stem cell
markers including LGR5 and Msi1 and can generate the adult epithelium expressing
IFABP. Thus, the cross talk with nonepithelial tissues is essential for adult stem cell de-
velopment. BL, basal lamina; PY, pyronin Y.
et al., 2007; Heimeier et al., 2010; Shi & Brown, 1993
). As mentioned ear-
lier, expression and functional analyses of TH response genes should be in-
formative for characterizing the niche factors. Although such analyses are
now in progress, there is accumulating evidence that some key signaling
pathways regulate the adult stem cells through interactions between the ep-
ithelium and the connective tissue.
5.1. MMPs and juxtacrine signaling
Matrix metalloproteinases (MMPs), a superfamily of Zn-dependent proteases,
are generally known to degrade various extracellular matrix (ECM) compo-
nents (
Birkedal-Hansen et al., 1993; Matrisian, 1992; McCawley &Matrisian,
2001; Woessner, 1991
). So far, a number of MMPs including collagenase-3, 4
(
Stolow et al., 1996
), gelatinase A, B (
Fujimoto, Nakajima, & Yaoita, 2006
),
stromelysin-3 (ST3; MMP11) (
Patterton, Hayes, & Shi, 1995
), and mem-
brane type-1-MMP (
Hasebe, Hartman, Matsuda, & Shi, 2006
)havebeen
identified as TH response genes in the
X. laevis
intestine (
Shi & Brown,
1993
) and are noteworthy in connection withmodification of the basal lamina
consisting of ECM components. Among such MMPs, ST3 is the only one
whose function has been demonstrated to modify the basal lamina structure
both
in vivo
(
Fu et al., 2005
)and
in vitro
(
Ishizuya-Oka et al., 2000
).
