Epigenetic Control of Animal Development - Building the Most Complex Structure on Earth - page 173

the flatworm Schmidtea mediterranea leads to smaller degrown phenotypes similar
to those produced by starvation ( Miller and Newmark, 2012 ).
The evidence presented above points to the existence in the brain of insects and
worms of set points that determine their characteristic body size. This evidence sug-
gests these invertebrates somehow perceive the actual body size and assess it. When
body size reaches the species-specific set point, the specialized neurons suppress or
reduce the secretion of insulin-like neuropeptides, and animals cease growing.
How Long Animals Live—An Epigenetic Decision
The same insulin-like neuropeptides that determine animal growth negatively regu-
late life span and aging in animals. C. elegans has 37 genes that secrete insulin-
like neuropeptides, some of which appeared approximately 600Mya, and others
evolved later through gene duplication ( Nelson and Padget, 2003 ). Most evidence
in this regard comes from the soil nematode worm Caenorhabditis elegans and
Drosophila , but basic mechanisms seem to have been conserved across the animal
world.
Under normal conditions, C. elegans development goes through four larval stages
before adulthood. But, in a dramatic move, under challenging conditions (scarce
food resources, crowding, high temperature, etc.), the worm halts at the third larval
stage, switching to an alternative developmental program, or dauer (from German
dauer , steady, permanent), to extend its life ( Figure 3.42 ).
Crowding is the primary cue for switching to the dauer mode and delaying age-
related physiological decline. These worms normally secrete a dauer pheromone
(consisting of a number of components), and crowding leads to an increased con-
centration of the pheromone in the environment. Responding to this higher phero-
mone concentration, the worm shifts to dauer mode. It assesses the availability of
food resources from the content of food odorants, as perceived by olfactory neurons.
This is demonstrated by the fact that in the presence of these odorants, even in the
absence of food, the worm switches to dauer mode.
During dauer, which may last for months, C. elegans stops food intake, reduces
metabolism, and becomes resistant to external factors, including oxidative stress.
The perception of unfavorable environmental factors (and especially detection by
olfactory neurons of the dauer pheromone) indicating crowding are crucial for the
switch to the dauer life cycle.
The worm has an extremely simple nervous system, consisting of only 302 neu-
rons. The sensory input on environmental conditions is received by ciliated sensory
neurons ASI, ADF, and ASG in the amphids (paired sensory organs in the head of
the worm). Integrating the environmental stimuli into the amphid neurons induces
the secretion of the neurotransmitter serotonin, which activates an insulin-like signal-
ing by ASI and ASJ neurons and TGF-β by ASI neurons. Removal of these neurons
causes growth to stop and the dauer program to be adopted, even in the presence of
food ( Fielenbach and Antebi, 2008 ), indicating that they are responsible and neces-
sary for adopting the dauer program.