Rise of the Animal Kingdom and Epigenetic Mechanisms of Evolution - Building the Most Complex Structure on Earth - page 283

mechanism and the only demonstrated mechanism of spatial restriction of expression
of hormonally induced genes (see page 200, Restricting Gene Expression to Relevant
Cells Alone: Binary Neural Control of Gene Expression ).
A clear example of the global neural control gene expression is the regulation of
muscle growth in insects. Muscle growth in insects results from the action of two
antagonistically acting neural hormones, the muscle growth-inducing insulin-like
peptides (Ilps) produced by a group of 14 neurons in the Drosophila brain, and mus-
cle growth-inhibiting neurohormone prothoracicotropic hormone (PTTH) secreted
by several other neurons ( Géminard et al., 2006 ).
A signal cascade originating in the hypothalamus also controls and regulates the
muscle growth in vertebrates. Based on the processing of afferent signals on the
state of muscle growth and other internal stimuli, such as nutritional status and exer-
cise, one of the two alternative hypothalamic neurotransmitter pathways (and other
extrahypothalamic pathways) ( Jorgensen et al., 1993; Ruaud and Thummel, 2008 ) is
activated:

●

Secretion of growth hormone-releasing hormone (GHRH) by a group of hypothalamic
neurons.

●

Secretion of its antagonist growth hormone releasing-inhibiting hormone (GHRIH) or
somatostatin.

Each of the neurohormones binds to its specific receptors in pituitary cells. The
first (GHRH) stimulates the secretion of growth hormone (GH), while the second
(GHRIH) inhibits GH secretion. GH stimulates muscle formation or growth and
secretion of insulin-like growth factor-1 (IGF-1), which is synergistic with GH.
Since the early 1980s it was demonstrated that the distribution pattern of myo-
blasts in sites of future muscles is determined by local innervation patterning of
segmental muscles in Drosophila ( Currie and Bate, 1991; Lawrence and Johnston
1984 ). The denervation of muscles in Manduca sexta prevents proliferation and
migration of myoblasts to the proper sites causing formation of muscleless legs
( Consoulas and Levin, 1997 ).
Experiments of denervation of indirect flight muscles in M. sexta have shown that:

The motoneuron influences both the number of cells available for fusion, as well
as potentially regulates the fusion events themselves. This in our view is an elegant
mechanism for controlling muscle fiber differentiation during myogenesis, and may
have evolved as a way to ensure that muscle primordial develops into muscles that
meet the diverse demands placed on them by the nervous system.
Fernandes and Keshishian (2005)

The dorsal external oblique (DEO1) muscle in M. sexta larvae consists of five
muscle fibers, but out of them one is lost and the surviving fibers develop into the
adult DEO1. Experiments of Hegstrom and Truman revealed that before ecdysis, the
terminal arbor of the local motoneuron withdraws from all the fibers but the one that
develops into adult DEO1. It was also found that in the absence of the motoneuron,
muscle cells express the ecdysone receptor EcRA, which causes muscle fibers' apop-
tosis. The muscle fiber that is innervated expresses the EcR-B1, which allows the