Epigenetic Control of Animal Development - Building the Most Complex Structure on Earth - page 171

serotonin in response. The serotonin starts a signal cascade that leads to decreased
sympathetic activity and consequent osteoblast proliferation and bone growth.
The local mechanism relies on the intense presence in bones of nerve endings,
which release in bones a number of neurotransmitters and neuropeptides, such as
serotonin, glutamate, catecholamine, vasoactive intestinal peptide (VIP), substance
P (SP), neuropeptide Y (NPY), calcitonin-gene-related peptide (CGRP), etc., which
are involved in bone formation and bone resorption ( Lerner, 2002; Lundberg et al.,
2000; Yeh et al., 2002 ).
How Animals Know When to Stop Growing—The Body
Size Set Point
Thus far, we have dealt with the development of various organs and structures from
a purely qualitative view, without considering the determination of the size or the
limits of growth, an equally important aspect of development. Body size is a typical
quantitative trait, and we will review briefly the mechanisms determining body size
in animals, both in invertebrates and vertebrates.
Drosophila , the old workhorse of biological investigation, is one of the insects in
which the mechanisms of neural control of body size are better known. During larval
stages, Drosophila's growth is stimulated by the secretion of seven types of insulin-
like neuropeptides, which come from seven median secretory neurons in the pars
intercerebralis of its protocerebrum. Their receptors mediate the growth-stimulating
effect of these neuropeptides. Ablation of these neurons reduces body size and the
number of cells in the adult insect.
In some insects, the brain assesses the body size based on the information it
receives from proprioceptors on the stretch caused by body growth. Increasing the
stretch beyond a species-specific, neurally determined set point, as assessed by
the insect's brain, signals for specific neurons to secrete allatostatins, which inhibit
the secretion of the juvenile hormone (JH) by corpora allata. The same signal stimu-
lates other neurons to secrete the neuropeptide PTTH, which induces secretion of the
ecdysis hormone ecdysone by the prothoracic gland (PG). In higher dipterans, both
the prothoracic gland and corpora allata are parts of a compound structure called
the ring gland ( Figure 3.41 ). Ecdysone and insulin-like neuropeptides (ILPs) have
antagonist effects, and the silence of the ecdysone receptor (EcR), the mediator of
the ecdysone growth-inhibiting action, leads to the production of larger Drosophila
offspring ( Colombani et al., 2005 ).
It is also suggested that larval growth stops when PG reaches a critical size and
the higher level of ecdysteroids induces expression of the early gene for the tran-
scription factor E74 and the beginning of the patterning of imaginal disks by
ecdysone ( Mirth et al., 2009 ).
Now we know that at a higher level of the neuroendocrine hierarchy of the neural
regulation of body size, production of Drosophila ILPs (DILPs) is regulated by the
secretion of the neurotransmitter serotonin (5-HT 1A ), which, via its receptor, inhibits
the secretion of DILP-2 by ILP neurons ( Luo et al., 2012 ).