Biology Reference
In-Depth Information
The major epithelial cells are intestinal absorptive cells possessing the brush
border that is much longer than that of the adult intestine (
Bonneville, 1963;
Fox, Bailey, & Mahoney, 1972
). Although a small number of proliferating
cells are randomly distributed in the larval epithelium (
Ishizuya-Oka &
Ueda, 1996; Marshall & Dixon, 1978a
), no undifferentiated cells are mor-
phologically identified by light and electron microscopy.
During metamorphosis, the small intestine rapidly shortens and remodels
from the larval to adult form (
Ishizuya-Oka & Shimozawa, 1987a; Marshall &
Dixon, 1978b
). At the early metamorphic climax (stage 60) (
Nieuwkoop &
Faber, 1967
), when the plasma level of TH becomes high (
Leloup &
Buscaglia, 1977
), most of the larval epithelial cells (larval proper cells) begin
to undergo apoptosis (
Ishizuya-Oka & Ueda, 1996
). At the same time, a small
number of undifferentiated cells become morphologically detectable as small
islets between the larval proper cells and the connective tissue in the entire
small intestine (
Hourdry & Dauca, 1977; McAvoy & Dixon, 1977
). These
cells are strongly stained red with pyronin Y (PY) (
Ishizuya-Oka & Shi,
2007
), actively proliferate, and gradually replace the larval proper cells under-
going apoptosis (
Ishizuya-Oka et al., 1997
). Then, with the progress of intes-
tinal fold formation, they differentiate into a single layer of the secondary
(adult) epithelium (
Hourdry & Dauca, 1977; McAvoy & Dixon, 1977
). After
the completion of metamorphosis (stage 66), the adult epithelium continu-
ously undergoes cell renewal along the trough-crest axis of multiple intestinal
folds (
Shi & Ishizuya-Oka, 1996
). That is, the epithelial cells proliferate in the
trough region of the folds and, as they migrate upward, gradually differentiate
into major absorptive cells, which possess the shorter brush border and express
intestinal fatty acid binding protein (IFABP), goblet cells, and enter-
oendocrine cells (
Ishizuya-Oka et al., 1997; McAvoy &Dixon, 1978
). Finally,
they undergo apoptosis at the tip of the folds (
Ishizuya-Oka & Ueda, 1996
).
These chronological observations imply that the undifferentiated cells stained
red with PY at stage 60 are adult progenitor cells that include multipotent stem
cells. Consistent with this, previous immunohistochemical and
in situ
hybrid-
ization analyses have shown that the adult progenitor cells express sonic
hedgehog (Shh) (
Hasebe, Kajita, Shi, & Ishizuya-Oka, 2008; Ishizuya-Oka
et al., 2001
), Musashi-1 (Msi1) (
Ishizuya-Oka et al., 2003
), phosphorylated
form of phosphatase and tensin homolog (P-PTEN), Akt (
Ishizuya-Oka &
Shi, 2007
), and protein arginine methyltransferase 1 (
Matsuda & Shi, 2010;
Shi, Hasebe, Fu, Fujimoto, & Ishizuya-Oka, 2011
), all of which are also
expressed in adult stem cells and their descendants of the mammalian intestine
(
de Santa Barbara, van den Brink, & Roberts, 2003; He et al., 2007; Kayahara
