Biology Reference
In-Depth Information
Differentiation of adult epithelium
LE
Adult progenitor/
stem cell
Shh
Cell contacts
Ptc, Smo, Glis
ST3
BMP4
TH
F
Chordin
Tolloid/BMP1
Figure 11.5 Thyroid hormone-induced signaling pathways leading to establishment of
the stem cell niche in the amphibian intestine during metamorphosis. Thyroid hormone
(TH) directly upregulates Shh expression specifically in adult progenitor/stem cells and
ST3 expression in fibroblasts (F). Shh acts only on nonepithelial tissues in a paracrine
manner and, together with TH, enhances the expression of other Shh pathway compo-
nents including Ptc, Smo, and Glis. Shh not only activates proliferation of the fibroblasts
but also upregulates their expression of BMP4, which in turn promotes differentiation of
the adult epithelium and/or maintains the adult stem cells under the control of TH-
upregulated expression of Tolloid/BMP1 through degrading Chordin. However, ST3
modifies the basal lamina and allows the fibroblast to make contact with the epithelial
cells, leading to activation of juxtacrine signaling involved in adult stem cell develop-
ment. In addition, these Shh/BMP4 and ST3 signaling pathways interact with other path-
ways such as Wnt one and are integrated to establish the stem cell niche. Arrows and
T-shaped bars indicate activation and repression, respectively.
6. EVOLUTIONARY CONSIDERATION AND PROSPECT
Amphibian metamorphosis shares common characteristics with mam-
malian birth, since the both phenomena are closely associated with adapta-
tion from aquatic to terrestrial life (
Shi, 1999; Tata, 1993
). Indeed, as the
amphibian intestine remodels during metamorphosis, the mammalian intes-
tine matures for the dietary transition during the peak of endogenous TH
levels around birth (
Plateroti, Kress, Mori, & Samarut, 2006; Sirakov &
Plateroti, 2011
). The expression of both ST3 (
Heimeier et al., 2010
) and
Shh (
Kolterud et al., 2009
) is also significantly upregulated in the mammalian
intestine, concomitantly with the increase of the TH levels. It should be
