This session discusses: 1. Development of the skeletal system 2. Development of the muscular system 3. Development of the pharyngeal apparatus

1. • The Skeletal System
• The Skull
• The Limbs
• The Vertebrae and Sternum
• The Muscular System
• The Pharyngeal Apparatus

2.  The skeletal system is derived from condensation of mesenchyme formed from three sources:
 Paraxial mesoderm: the ventromedial portion of the somites, called the sclerotome forms
mesenchyme which can produce fibroblasts, chondroblasts, and osteoblasts
 Somatic lateral plate mesoderm: also forms mesenchyme which contributes to the bones of the
shoulder and pelvic girdles in addition to the bones of the limbs
 Neural crest cells: forms mesenchyme which contributes a large portion of the bones of the skull

3.  Bones are formed either by intramembranous ossification or by endochondral ossification:
 Intramembranous ossification is the formation of bone from membranous sheaths formed from mesenchyme; it
occurs mainly in the flat bones of the skull
 Endochondral ossification is the replacement of hyaline cartilage by bone cells; it occurs in most long bones

4.  The skull is divided into two parts: the viscerocranium (facial skeleton) and the neurocranium (skull
base and case)

5.  The viscerocranium is derived from the neural crest cells of the 1st and 2nd pharyngeal arches; the
first arch forms a dorsal portion, the maxillary process, which extends forward beneath the eye region
to form the maxilla, zygomatic bone, and part of the temporal bone
 It also gives rise to a ventral portion, the mandibular process, which contains Meckel’s cartilage
surrounded by mesenchyme; the mesenchyme undergoes intramembranous ossification to form the
mandible; most of Meckel’s cartilage disappears except for the sphenomandibular ligament
 The dorsal tip of the mandibular process and that of the 2nd pharyngeal arch later form the three
bones of the middle ear: incus and malleus from 1st arch, and stapes from the 2nd arch

6.  The neurocranium is composed of two parts: the membranous part (which forms the protective case
around the brain) and the cartilaginous part (or chondrocranium, which forms the skull base)
 The chondrocranium is initally composed of a number of separate cartilages that later fuse to form the
skull base; the mesenchyme for these cartilages is derived from two sources:
 Those cartilages that lie ventral to the cranial end of the notochord are derived from neural crest cells, and this
portion is called the prechordal chondrocranium
 Those that lie dorsal to this end of the notochord are derived from the sclerotome of the occipital somites, and
this portion is called the chordal chondrocranium
 Later these cartilages are replaced by bone tissue by endochondral ossification

7.  The membranous neurocranium is derived from two sources: neural crest cells and paraxial
mesoderm; they form mesenchyme which invests the brain and undergoes intramembranous
ossification; this begins by bone spicules that radiate from the primary ossification centers; the bones
continue to enlarge by deposition of new bone tissue on the outside, and resorption of old bone
tissue from inside by the osteoclasts

8.  The membranous neurocranium is derived from two sources: neural crest cells and paraxial
mesoderm; they form mesenchyme which invests the brain and undergoes intramembranous
ossification; this begins by bone spicules that radiate from the primary ossification centers; the bones
continue to enlarge by deposition of new bone tissue on the outside, and resorption of old bone
tissue from inside by the osteoclasts

9.  At birth, the flat bones of the skull are separated by seams of connective tissue called sutures, which
are derived from the same two sources: neural crest (sagittal suture) and somites (coronal suture);
when more that two bones meet, sutures are wider and are called fontanelles; the anterior fontanelle
closes after about 1 year and a half after birth, while the posterior one closes after one year
 These sutures and fontanelles have many benefits:
 During delivery, they allow the flat skull bones to mold over each other and allow the large head of the fetus to
pass through the uterine canal
 They allow enlargement of the brain with age
 For the initial years of life, palpation of the anterior fontanelle gives valuable information as to whether skull
ossification is normal or not, and whether intracranial pressure is normal

10.  Initially the size of the face is small compared with the skull; this is caused by:
 Absence of paranasal air sinuses in the bones
 Small size of the jaws
 With appearance of the teeth and air sinuses, the face becomes larger

11.  Development of limbs begins by formation of limb buds as outpocketings from the ventrolateral body
wall, composed of a core of mesenchyme (from somatic lateral plate mesoderm) covered by
ectoderm; the mesenchyme forms the bone and connective tissue (but not the muscle) while the
ectoderm forms the epidermis of the skin
 The ectoderm at the distal border of the bud is known as the apical ectodermal ridge (AER) and has
inductive influence on the underlying mesenchyme to form a progress zone, composed of
undifferentiated and rapidly proliferating cells that elongate the limb; mesenchyme far away from
the influence of the AER begins differentiating into bone; limb development proceeds proximodistally

12.  Later the terminal part of the limb flattens to form the hand- or foot-plate; then a circular constriction
separates this portion from the rest of the limb and another constriction separates the proximal part
into two parts, thus forming the characteristic parts of the adult limbs
 Fingers form by four areas of cell death in the AER to form five digits which elongate by continuous
growth; development of upper limb is ahead of that of the lower limbs by 1 to 2 days; later the upper
limbs rotate laterally 90o to place the thumb laterally and extensor muscles posterolaterally, while
lower limbs rotate medially 90o to place the big toe medially and extensor muscles in front

13.  In addition to development of external shape, the underlying mesenchyme condenses in certain areas
then undergoes chondrification; first hyaline cartilage models are present by the 6th week

14.  Joints are formed in joint interzones where chondrocytes increase in number and density, then the
central cells undergo cell death forming the joint cavity while the peripheral cells form the joint
capsule, ligaments, and synovial membrane

15.  Endochondral ossification of long bones of the limbs begins by the end of the embryonic period and
primary ossification centers are present in the diaphysis of all the long bones by the 12th week;
ossification begins in the diaphysis of the bone and proceeds towards both extremities; at birth
diaphysis is usually completely ossified but the epiphysis are still cartilaginous
 Secondary ossification centers then appear in the epiphysis; an epiphyseal plate of cartilage remains
between the ossified diaphysis and epiphysis and allows further elongation of bones; bone growth
stops when this plate disappears and the diaphysis and epiphyses fuse (completed by the age of 20)

16.  A typical vertebra consists of a vertebral arch, vertebral foramen, body, transverse processes, and a
spinous process
 Vertebrae form from the sclerotome portion of the somites, which migrate around the neural tube
and notochord and join with those of the opposing somites

17.  The fused sclerotome portions of the two sides, around the neural tube and notochord, undergo a
process of resegmentation, in which the cranial half of each segment of fused sclerotome grows into
and fuses with the caudal half of its adjacent segment; the vertebrae form from this new combination
 The mesenchyme in the center of the original sclerotome portions does not proliferate and remains
between the new precartilaginous vertebral bodies to contribute to intervertebral discs; the
notochord disappears in the vertebral bodies entirely, but persists in the region between them to
later form the nucleus pulposus, surrounded by annulus fibrosus to form the intervertebral disc

18.  As a result of resegmentation:
 The myotomes bridge the intervertebral discs which gives them the capacity to move the spine
 The intersegmental arteries pass midway over the vertebral bodies
 The spinal nerves lie near the intervertebral discs and leave the vertebral column through the intervertebral
foramina

20.  Ribs develop from the costal processes of the thoracic vertebrae, and thus are derived from the
sclerotome portions of the thoracic somites
 The sternum is derived from two vertical mesenchymal bands in the ventrolateral body wall derived
from the somatic lateral plate mesoderm; these bands grow medially until they begin to fuse
craniocaudally to form the manubrium, sternebrae, and the xiphoid process

21.  The muscular system is mainly derived as follows:
 Skeletal muscles from paraxial mesoderm (i.e. somites)
 Smooth muscle from splanchnic mesoderm
 Cardiac muscle from splanchnic mesoderm (from the cardiac progenitor cells)
 Smooth muscle in the wall of dorsal aorta, large arteries, and coronary arteries also derives from
neural crest cells; in addition, pupillary muscles, mammary gland muscles, and sweat gland muscles
are derived from ectoderm

22.  Skeletal muscles are derived from somites (i.e. paraxial mesoderm); the ventrolateral lip (VLL) of the
dermomyotome forms the hypomere (or hypaxial musculature) which develops into the ventral
muscles of the body; the dorsomedial lip (DML) of the dermomyotome forms the epimere (or
epimeric musculature) which develops into the muscles of the back
 These cells differentiate into myoblasts, which fuse to form muscle fibers which later develop
myofibrils and cross-striations; tendons for the muscles are derived from sclerotome
 Patterning of muscle formation is controlled by the connective tissue into which the myoblasts
migrate: neural crest cells (head region), somites (cervical and occipital regions), and lateral plate
mesoderm (body wall and limbs)

23.  The epimere gives rise to the extensor muscles of the vertebral column

24.  Cervical hypomere gives rise to scalene, geniohyoid and prevertebral muscles

25.  Cervical hypomere gives rise to scalene, geniohyoid and prevertebral muscles

26.  Cervical hypomere gives rise to scalene, geniohyoid and prevertebral muscles

27.  Thoracic and abdominal hypomere is separated into three layers at the ventrolateral body wall;
because of the presence of the ribs, the thoracic hypomere cells retain their segmental character,
while the abdominal hypomere cells fuse to form large sheets of muscle

28.  Thoracic hypomere gives rise to external intercostals, internal intercostals, and innermost
intercostals (or transversus thoracis)

29.  Thoracic hypomere gives rise to external intercostals, internal intercostals, and innermost
intercostals (or transversus thoracis)

30.  Thoracic hypomere gives rise to external intercostals, internal intercostals, and innermost
intercostals (or transversus thoracis)

31.  Abdominal hypomere gives rise to the external oblique, internal oblique, and transversus abdominis

32.  In addition to all the previous muscle derivatives, a ventral longitudinal band of hypomere develops at
the ventral body wall which gives rise to: infrahyoid muscles (in the neck), rectus abdominis (in the
abdomen) and a variable sternalis muscle (in the thorax)

33.  In addition to all the previous muscle derivatives, a ventral longitudinal band of hypomere develops at
the ventral body wall which gives rise to: infrahyoid muscles (in the neck), rectus abdominis (in the
abdomen) and a variable sternalis muscle (in the thorax)

34.  In addition to all the previous muscle derivatives, a ventral longitudinal band of hypomere develops at
the ventral body wall which gives rise to: infrahyoid muscles (in the neck), rectus abdominis (in the
abdomen) and a variable sternalis muscle (in the thorax)

35.  Lumbar hypomere cells give rise to the quadratus lumborum muscle

36.  Hypomere from the sacral and coccygeal regions forms the pelvic diaphragm and striated muscles of
the anus

37.  All the muscles of the head are derived from paraxial mesoderm (somitomeres and occipital somites);
patterning is directed by neural crest cells; the only exception is the pupillary muscles derived from
the optic cup ectoderm

38.  Bones of the limbs are derived from somatic lateral plate mesoderm, while the muscles are derived
from the hypomere myotomes of the somites; muscle tissue then splits into flexor and extensor
compartments, and later fuse to form large muscles derived from several segments

39.  Upper limb buds lie opposite C4-T2 segments, while lower limb buds lie opposite L2-S2 segments;
ventral primary rami from the corresponding spinal nerves penetrate the buds; initially having
separate ventral and dorsal branches, later the branches of different nerves join to form larger nerves
like radial, ulnar, and median nerves (for the upper limb) which establish intimate contact with the
differentiating muscle mesenchyme; this contact is essential for complete functional differentiation,
motor innervation, and sensory innervation of the developing muscles

40.  Cardiac muscle (myocardium) is derived from the splanchnic mesoderm surrounding the endocardium
(derived from cardiac progenitor cells); myoblasts don’t fuse but adhere to one another by special
attachments (later forming intercalated discs); later some muscle cells with fewer myofibrils and
larger diameter become Purkinje fibers

41.  Smooth muscle is derived as follows:
 In the wall of the gut and its derivatives, it is derived from the surrounding splanchnic lateral plate mesoderm
 In the wall of dorsal aorta and large arteries, it is derived from lateral plate mesoderm and neural crest cells
 In the wall of coronary arteries, it is derived from neural crest cells and proepicardial cells
 The exceptions from smooth muscles are the pupillary muscles, sweat gland muscles, and mammary
gland muscles which are derived from ectoderm

42.  Mesenchyme for the development of the head region is derived from paraxial and lateral plate
mesoderm, neural crest cells, and ectodermal placodes
 Six pharyngeal arches begin to form in the head and neck region in a craniocaudal sequence; these
arches are bars of mesenchyme covered by ectoderm externally and endoderm internally; they are
separated by pharyngeal clefts externally, and later by pharyngeal pouches internally; since the
pouches and clefts don’t establish contact, fish gills (branchia) are never formed in humans
 From each arch, muscle component is derived from the paraxial mesoderm, bone component from
neural crest, paraxial mesoderm, and lateral plate mesoderm; each arch has its own cranial nerve, and
its own artery

43.  Each pharyngeal arch has its own arterial branch, which arises from the aortic horns and passes
backward through the arch mesenchyme to reach the ipsilateral dorsal aorta

44.  1st Arch: It has a dorsal maxillary process which forms the maxilla, zygomatic bone, and part of
temporal bone; the ventral mandibular process forms Meckel’s cartilage, which gives rise to the
incus, malleus, the anterior ligament of malleus, and the sphenomandibular ligament; the mandible
forms by intramembranous ossification and not from Meckel’s cartilage

45.  2nd Arch: It gives rise to Reichert’s cartilage which forms the stapes, styloid process of the temporal
bone, stylohyoid ligament, lesser horn of hyoid bone, and the upper part of the body of hyoid bone
 3rd Arch: It forms the greater horn and the lower part of the body of hyoid bone

46.  4th and 6th Arches: They fuse to form all of the laryngeal cartilages (thyroid, cricoid, arytenoid,
corniculate, and cuneiform) except for the epiglottis (derived from hypopharyngeal eminence)
 5th Arch: It is rudimentary with no derivatives

50.  The epiglottis is derived from the hypopharyngeal eminence which is a swelling formed by the
mesenchyme of the 3rd and 4th arches on the floor of the embryonic pharynx

52.  Each has its cranial nerve which supplies the connective tissue and muscles derived from the arch; the
nerves are: mandibular and maxillary divisions of the trigeminal nerve (1st arch), facial nerve (2nd
arch), glossopharyngeal nerve (3rd arch), superior laryngeal branch of vagus nerve (4th arch) and
recurrent laryngeal branch of vagus nerve (6th arch)

53.  1st Arch: It gives rise to the muscles of mastication (medial and lateral pterygoids, masseter, and
temporalis), mylohyoid, anterior belly of digastric, tensor tympani, and tensor veli palatini
 2nd Arch: It gives rise to muscles of facial expression, stapedius, stylohyoid, posterior belly of
digastric, and auricularis muscles

54.  3rd Arch: It gives rise to the stylopharyngeus
 4th Arch: It gives rise to the cricothyroid, levator veli palatini, and pharyngeal constrictors
 6th Arch: It gives rise to all the intrinsic muscles of the larynx (except cricothyroid)

55.  Five pharyngeal pouches appear in a craniocaudal sequence between the pharyngeal arches; the fifth
pouch may be considered rudimentary and its derivative is included in those of the 4th pouch
 The 1st pouch is called the tubotympanic recess; its endoderm approches the epithelium of the first
pharyngeal cleft (or groove) and later they form the tympanic membrane; the distal part of the recess
forms the middle ear (or tympanic) cavity while the proximal portion forms the eustachian tube
 The endoderm of the 2nd pouch proliferates and forms buds that penetrate the surrounding
mesenchyme to form the crypts of the palatine tonsils; later the mesenchyme forms lymphatic tissue
which invades the tonsils; the remnant of the pouch itself is visible as the tonsillar fossa

56.  The distal part of the 1st pouch forms the middle ear cavity while the proximal portion forms the
eustachian tube; the 2nd pouch gives rise to the palatine tonsil and persists as the tonsillar fossa

57.  The 3rd and 4th pouches have dorsal and ventral wings; the dorsal wing of the 3rd pouch forms the
inferior parathyroid gland while the ventral wing forms the thymus; the thymus detaches from the
pharyngeal wall and migrates caudomedially taking the inferior parathyroid with it until it rests in the
anterior thorax while the inferior parathyroid lies on the dorsal aspect of the thyroid gland
 The dorsal wing of the 4th pouch forms the superior parathyroid glands; the ventral wing is used to
refer to the 5th pharyngeal pouch which forms the ultimobranchial bodies that are incorporated into
the thyroid gland to form the parafollicular or C cells which secrete calcitonin

60.  Four pharyngeal clefts (or grooves) appear externally between the first five pharyngeal arches; the 1st
cleft penetrates the underlying mesenchyme to form the external auditory meatus, and its epithelial
lining establishes contact with the endoderm of the 1st pouch to form the tympanic membrane
 Proliferation of the mesenchyme of the 2nd arch causes it to overlap the 3rd and 4th arches and fuse
with the epicardial ridge; thus the remaining three clefts temporarily form a closed ectoderm-lined
cervical sinus which later disappears