Epigenetic Control of Animal Development - Building the Most Complex Structure on Earth - page 154

larval muscle fibers. The fact that the innervation by the motoneuron is responsible
for the expression of EcR-B1 is also demonstrated by the experimental denervation
of muscle fibers that leads to the dramatic reduction and full repression of EcR-B1
expression ( Hegstrom et al., 1998 ).
It is true that in insects, muscle development usually requires ecdysone regulation
along the innervation, but as is well known, ecdysone secretion is itself under strict
regulation by the CNS (primarily by the neuropeptide PTTH).
Myogenesis in Vertebrates
Somites are transient structures from which the skeleton and muscles develop.
The formation of muscles is one of the earliest results of the neural tube inductive
actions in somites. In Xenopus laevis , the development of myotome and muscles
from somites requires Wnt signals from the dorsal neural tube and Shh and sig-
nals from the ventral neural tube and the notochord ( Cossu and Borello, 1999 ; see
Figure 3.27 ).
The mediator of Wnt and Shh action in myogenesis is Pax 3, which induces the
expression of two myogenic genes, MyoD and Myf 5. Myogenesis in many animals is
primarily determined by the expression of transcription factors from the MyoD fam-
ily ( Myf 5 , MyoD , and myogenin) after somite formation ( Piran et al., 2009 ). A sim-
plified gene regulatory network for the initiation of myogenesis and chondrogenesis
is presented in Figure 3.28 .
As noted above, Shh and Wnt signals for the expression of MyoD genes originate
in the neural tube, as demonstrated by the fact that somites do not express MyoD
genes when separated from the neural tube ( Alves et al., 2003 ) and experimental
misexpression of MyoD and Myf5 in the chick neural tube induces the development
of ectopic skeletal muscles ( Delfini and Duprez, 2004 ). Signals from the dorsal neu-
ral tube, and to a lesser extent from the ventral neural tube, are basic inducers of
myogenesis and the ablation of the neural tube prevents the formation of muscles in
somites ( Stern, 2005 ). In chick embryos, the neural tube regulates the directed elon-
gation of myocytes; removal of half of the neural tube at the presomitic mesoderm
level, before differentiation of myocytes, causes disorganization of myocytes in com-
parison with the control side after 24 h ( Gros et al., 2009 ).
Denervation leads to the upregulation and downregulation of 32 genes and to
muscular atrophy. The altered expression of five of these genes indicates that Wnt
signaling may be reduced after denervation ( Magnusson et al., 2005 ). Denervation
leads to the increased expression of the myogenin gene ( Voytik et al., 1993 ), sug-
gesting that the nervous system may also act as a brake in muscle development,
probably by determining the growth rate and/or the end of muscle growth.
Examples of the direct influence of the CNS and local innervation on muscle
development in vertebrates are plentiful. In electrical fish, innnervation is neces-
sary for the transformation of muscle fibers into electrocytes, and the interruption
of neural input causes the dedifferentiation of electrocytes back into muscle fibers