Biology Reference
In-Depth Information
There has been some recent progress on the study of how cell growth
arrest is regulated in dying salivary glands. The evolutionarily conserved
Warts (Wts)/Hippo (Hpo) signaling pathway is an important negative reg-
ulator of cell growth that functions through the inactivation of Yorkie (Yki),
a transcriptional coactivator and positive regulator of growth (
Huang, Wu,
Barrera, Matthews, & Pan, 2005
). Loss-of-function mutations in the Wts
pathway or overexpression of Yki lead to tissue overgrowth (
Huang
et al., 2005
). Importantly,
wts
is required for growth arrest and autophagy
induction in degrading salivary glands (
Dutta & Baehrecke, 2008
). Disrup-
tion of this pathway by mutations in
wts
and
hpo
or knockdown of
sav
and
mats
prevents salivary gland degradation (
Dutta & Baehrecke, 2008
). Sur-
prisingly, overexpression of Yki fails to inhibit salivary gland degradation,
suggesting that Wts regulates salivary gland growth in a Yki-independent
manner. Significantly,
wts
mutants cause persistent class I PI3K signaling
in salivary glands, and knockdown of
chico
or expression of dominant-
negative TOR suppresses the
wts
cell death defects (
Dutta & Baehrecke,
2008
). These data suggest that Wts regulates salivary gland cell growth in
a class I PI3K-dependent manner. However, Wts does not have a common
role in programmed cell death. Despite the clear requirement for class I PI3K
signaling in the regulation of cell growth and cell death in the midgut,
knockdown of
wts
does not affect midgut morphology or degradation
(
Denton, Chang, et al., 2012
).
4.2. Autophagy and cell death
Programmed cell death is a highly conserved and genetically regulated fun-
damental biological process. During development, cell death is required for
tissue pattern formation and to maintain tissue homeostasis. Cell death also
functions to remove abnormal or damaged cells.
Schweichel and Merker
(1973)
described three major types of cell death during mammalian devel-
opment based on morphology and involvement of the lysosomal compart-
ment. Type I cell death, or apoptosis, is characterized by caspase activation,
cell shrinkage, cytoplasmic blebbing, nuclear and DNA fragmentation, and
engulfment by a phagocyte where the lysosome of the engulfing cell de-
grades the dying cell (
Kerr, Wyllie, &Currie, 1972
). In contrast to apoptosis,
type II cell death, or autophagic cell death, requires little or no help from
phagocytes, and the dying cell is degraded by its own lysosome. Type III
cell death, or necrosis, is the least common form of cell death, and it has
no known lysosomal involvement.
