Epigenetics of Reproduction in Animals - Building the Most Complex Structure on Earth - page 81

precisely restricted action of circulating inducers to relevant cells/organs alone is a
formidable challenge that no genecentric-prone approach can explain.
Metazoans evolved a binary neural control of gene expression, which makes pos-
sible local action of global circulating inducers. The system uses at least two mecha-
nisms of restriction:
1. Local innervation induces the expression of relevant receptors in target cells so that circu-
lating inducers can express specific genes in target cells alone.
2. Local innervation induces the expression of specific genes by releasing local gene inducers.
Let us consider only the signal cascade of the steroid hormone estrogen, which is
responsible for folliculogenesis, i.e., the growth and development of follicles. It starts
with hypothalamic neurons secreting neurohormone GnRH. Its secretion stimulates the
pituitary to synthesize gonadotropins, an FSH, and luteinizing hormone (LH). These
hormones induce sex glands to produce E2, which is essential for folliculogenesis and
the production of egg cells. How does the organism restrict the expression of E2 in the
ovary and, more precisely, in the granulose cells surrounding the ovarian follicle?
We know that this is possible from the release by the ovarian sympathetic nerve
endings of the neurotransmitters norepinephrine, vasoactive intestinal peptide (VIP),
or both. This stimulates granulosa cells to express the FSH receptor (the media-
tor of the gonadotropic functions of the pituitary FSH; see Figure 2.7 ). The local
innervation only “targets a circumscribed subpopulation of ovarian cells” ( Mayerhof
et al., 1997 ), the granulosa cells in the vicinity of developing follicles. Neonates that
underwent sympathectomy showed stunted folliculogenesis, reduced production of
E2, and delayed ovulation ( Lara et al., 1990; Riboni et al., 1998 ).
Figure 2.11 shows a schematic model of regulation of the muscle growth in
insects. As it shows, systemic signals for stimulating (Ilp neuropeptides) and inhibit-
ing (PTTH→ecdysone) myogenesis originate in the insect's brain.
In Manduca sexta , the larval dorsal external oblique (DEO1) muscle consists of five
muscle fibers, but as an adult, the insect remodels the muscle radically by eliminating
four muscle fibers and allowing only one to remain. During ecdysis, muscle growth in
insects stops because of ecdysone secretion, which inhibits muscle growth, but never-
theless, the surviving muscle fiber continues to grow. This is again neurally regulated:
the terminal arbor of the motoneuron innervating five larval DEO1 fibers recedes
from all but one of them, the surviving one, which then becomes the adult DEO1. The
remaining branch of the motoneuron induces the muscle fiber to express the recep-
tor ecdysone receptor B1 (EcRB1), which stimulates muscle growth ( Hegstrom and
Truman, 1996 ). The already uninnervated muscles express the isoform EcRA of the
ecdysone receptor, which stimulates programmed cell death, degeneration, and elimina-
tion of four larval muscle fibers.
Whether ecdysone will perform its antimyogenic action depends on the type of
receptor that will be expressed by the muscles. And the expression of EcRB1, which
is necessary for muscle growth, or EcRA, which leads to the inhibition of muscle
growth by ecdysone, depends on local innervation.
The binding of ligands (e.g., hormones and growth factors) to the cell surface
(integral extracellular) receptors marks the beginning of an intracellular cascade