Living and Adapting to Its Own Habitat - Building the Most Complex Structure on Earth - page 202

mechanism involves local nerves that induce expression of specific receptors in the
region they innervate. This remarkable mechanism of adjacent neural control of gene
expression complements the global neural control of gene expression performed by
the CNS, primarily via the hypothalamic-pituitary target endocrine gland axes.
This is a binary neural control of gene expression and is the only mechanism of spa-
tial restriction of gene expression known as of now ( Cabej, 2008, 2012, pp. 243-247 ),
which is of paramount importance for the life and evolution of metazoans.
Experimental evidence on the adjacent neural control of gene expression is still
modest for the simple reason that it was not on the researchers' agendas (rarely can
you expect to find something you are not looking for). But the evidence is certainly
adequate to demonstrate that the mechanism exists and evolution could not afford to
waste a mechanism of such paramount importance for development.
The binary neural control of gene expression is observed in both invertebrates,
suggesting that it may have evolved more than 500 million years ago, during the
Cambrian explosion.
Let us look at the mechanism as it unfolds in a few selected examples.
In the moth Manduca sexta (tobacco hornworm), the dorsal external oblique 1
(DEO1) muscle consists of five muscle fibers. During metamorphosis, not all but one of
these muscle fibers are lost. The surviving muscle fiber develops into the adult DEO1.
In 1996, Hegstrom et al. (1998) observed that the only difference related to the fate of
the surviving muscle fiber from the four others was that the axonal arbor of the moto-
neuron that innervates the larval DEO1 retracts from all the larval fibers except from the
one that eventually turns into the adult DEO1. Investigators explained why the action of
the circulating hormone ecdysone (ECD) is restricted to only one of the five fibers of
the DEO1 muscle: it is the only fiber that expresses the ECD isoform receptor EcR-B1:
Innervation regulates the choice of EcR isoforms expressed in growing muscle. This
choice may then determine the nature of the response of the muscle to changing ster-
oid titers.
Hegstrom et al. (1998)
Binding of circulating ECD to the receptor isoform EcR-B1 expressed by myo-
blasts of the muscle fiber stimulates their proliferation and survival to become the
adult DEO1. Myoblasts of the four other muscle fibers, which lost contact with
the axonal arbor of the motoneuron, express another isoform of the ECD receptor,
EcRA, which stimulates their programmed death and elimination. Thus, local inner-
vation determines that the circulating ECD performs its proliferating action on one
muscle fiber/myoblast but not on others. It is demonstrated, in both in vivo and in
vitro experiments, that local nerves perform their muscle-forming action by releasing
diffusible chemicals or by transmitting electrical signals ( Curie and Bate, 1991 ).
In 1999, Nijhout marveled on the subject:
It is as if tissues somehow “know” when the hormonal signal will come and become
receptive to it only at that time.
Nijhout (1999)