Biology Reference
In-Depth Information
period between critical weight and the cessation of feeding, known as the
terminal growth period (TGP). During this period the larva can quadruple
its size in nutrient rich environments (
Beadle, Tatum, & Clancy, 1938;
Edgar, 2006
). Since nutrition affects growth, but not developmental time
during the TGP, nutrient restriction during this period has a large impact
on final body size.
As critical weight relates to body size and not developmental time, there
must be a system that continuously assesses nutrient levels and growth status
to determine if critical weight has been attained. The insulin-like peptides
play a key role in determining critical weight, a genetically determined size,
and the outcome of surpassing this checkpoint is the production of a low-
level ecdysone pulse in early L3 (
Mirth & Riddiford, 2007; Mirth &
Shingleton, 2012; Rewitz et al., 2013
). Insulin-like peptides are ancient sig-
nal molecules that appear to play a conserved role in coordinating growth
and progression through life stages in animals. In both
Drosophila
and
C. elegans
these factors adjust systemic growth in response to environmental
conditions and relay information to the endocrine system to control timing
of steroid release and transition to the adult stage (
Tennessen & Thummel,
2011
). In
Drosophila
, disrupting insulin signaling before critical weight delays
puparation, but after surpassing this checkpoint reduced insulin signaling
affects growth and final size but not timing of metamorphosis
(
Shingleton, Das, Vinicius, & Stern, 2005
). This demonstrates that insulin
signaling is essential in setting the critical weight parameter.
2.2. Insulin/target of rapamycin (TOR) couples
nutrient-dependent growth to timing of maturation
In
Drosophila
, seven insulin-like peptides called DILP1-7 are believed to sig-
nal through a single insulin receptor (InR) of the receptor tyrosine kinase
family (
Ikeya, Galic, Belawat, Nairz, & Hafen, 2002; Rulifson, Kim, &
Nusse, 2002
). These
DILPs
are expressed in different tissues including the
gut, imaginal discs, fat body, glia cells, and neurosecretory cells of the brain,
known as the insulin producing cells (IPCs).
DILP2
,
DILP3
, and
DILP5
are
expressed in the IPCs which are the main source of circulating DILPs during
development and thought to be functionally equivalent to the mammalian
pancreatic islet
b
-cells. Genetic ablation of these cells causes severe reduction
in systemic growth and final adult size. Binding of the ligand to InR activates
a conserved intracellular network of signaling molecules including pho-
sphoinositide 3 kinase (PI3K) and AKT (
Fig. 2.2
). The activation of
AKT (also known as protein kinase B; PKB) promotes growth by
