Front Matter

48 Canine Sports Medicine and Rehabilitation

The mammalian musculoskeletal system
derives predominantly from mesoderm. During
development, mesoderm is established during
gastrulation, as cells of the deep surface of the
epiblast delaminate from the ectodermal
portion of the primitive streak to populate
the mesenchyme between the ectodermal and
endodermal germ layers. During neurulation,
these cells organize along the lateral aspects of
the developing neural tube to form the paraxial
mesoderm. Secretion of morphogens by cells of
the neural tube and adjacent ectoderm triggers
segmentation of the paraxial mesoderm into
somites. The ventromedial aspect of the somite
forms the sclerotome, from which vertebrae
and ribs derive. The dorsolateral aspect of the
somite forms the dermomyotome, which fur­
ther organizes into superficial dermotomal and
deep myotomal components. The cells of the
myotome undergo myoblastic differentiation
and give rise to the axial musculature. The lat­
eral aspect of the paraxial mesoderm develops
into the lateral plate mesoderm, which divides
into superficial somatic and deep splanchnic
layers (Figure 3.3). The limbs originate as focal
thickenings of the somatic lateral plate meso­
derm (limb buds). The early limb bud is popu­
lated by myoblastic cells that migrate into the
lateral plate mesoderm from the somitic
myotomes, and that ultimately give rise to the
appendicular musculature. Outgrowths of
cells  of the neural tube enter the limb bud in
conjunction with myoblasts to innervate
developing limb structures. Outward growth
and patterning of the limb is guided by
gradients of  signaling molecules produced
by the surrounding ectoderm.
Myoblastic differentiation within the
myotome is the earliest musculoskeletal fate
specification to occur during development.
Muscle development is triggered by the
activation of a myogenic transcriptional
program that culminates in the expression of a
core set of myogenic factors including myogenic
factor 5 (MYF5), muscle‐specific regulatory
factor‐4 (MRF‐4), myoblast determination pro­
tein (MYOD), and myogenin (Pownall et  al.,
2002). The timing and sequence of expression of
these myogenic factors varies with anatomic site
during development. Contractile myofibers
first  appear in the limbs at approximately
mid‐gestation, prior to limb innervation. These

primary fibers persist as type I (slow‐twitch, or

oxidative) fibers in the adult. Secondary

myofibers develop later concomitant with

the establishment of limb innervation and

become type II (fast‐twitch, or glycolytic) fibers.

(A)

(B)

(C)

LB

MT

DT

SC

DM

NC

N S LPM

Figure 3.3 Schematic cross‐sectional depiction of

embryological origins of musculoskeletal structure.

(A) Segmentation of paraxial mesoderm adjacent to the

neural tube (N) and notochord (NC) leads to the

formation of somites (S) and lateral plate mesoderm

(LPM). (B) Each somite segregates into a ventromedial

sclerotome (SC) and a dorsolateral dermomyotome (DM).

(C) The dermomyotome separates into a dorsolateral

dermatome (DT, red) and a ventromedial myotome

(MT, blue). Appendicular musculoskeletal structures

derive from mesodermal precursors that migrate into the

limb bud (LB) from the ventrolateral dermomyotome and

lateral plate mesoderm (arrows). Axial musculoskeletal

structures derive from the sclerotome.