development of muscles and integumentary system

1. DEVELOPMENT
OF MUSCULAR
SYSTEM
By
Dr saima

2.  The Muscular System develops from the
mesodermal germ layer, except some smooth
muscle tissue.

3. MUSCULAR SYSTEM
It consists of:
SKELETAL MUSCLE:
 Derived from paraxial mesoderm (somitomeres &
somites)
SMOOTH MUSCLE:
 Derived from splanchnic mesoderm surrounding the
gut and its derivatives, & from ectoderm (pupillary,
mammary gland & sweat gland muscles).
CARDIAC MUSCLE:
 Derived from splanchnic mesoderm surrounding the
heart tube.

4.  Muscle tissue develops from myoblasts,
embryonic muscle cells that are derived from
mesenchyme (embryonic connective tissue).

5. STRIATED SKELETAL
MUSCULATURE
 Somites and somitomeres
form the musculature of the
axial skeleton, body wall,
limbs and head.
 From the occipital region
caudally, somites
differentiate into
sclerotome, dermatome &
two muscle forming
regions.

6.  Dorsolateral region of the
somite expresses the muscle-
specific gene MYO-D and
migrates to provide progenitor
cells for limb and body wall
(hypomeric) musculature.
 Dorsomedial region,
migrates ventral to cells that
form the dermatome, and
forms the myotome. This
region, which expresses the
muscle-specific gene MYF5,
forms epimeric musculature.

7.  Border between somite and the parietal layer
of the lateral plate mesoderm called lateral
somatic frontier.
 Separate primaxial domain( around neural tube
---somite derived paraxial mesoderm
 Abaxial domain (lateral plate mesoderm +cells
of somite cross the frontier)
 Lateral somatic frontier define as border
between dermis derived from dermatomes in
the back and dermis derived from lateral plate
mesoderm in body wall
 Border of rib priaxial and cartilage is abaxial.

8. Origin of muscle from abaxial &
primaxial precursors
primaxial Abaxail
Cervical scalenes infrahyoid
Geniohyoid, prevertebral
Thoracoabdominal region intercostal Pectoralis major and minor
External and internal
abdominus
Transversus abdominus
Sternalis, rectus
abdominus,pelvic diaphragm
Upper limb Rhomboid, levator scapulae Distal limb muscles
Lower limb All lower limb muscles

9. Lateral
somatic
fontier

10. STRIATED SKELETAL
MUSCULATURE (cont’d)
 During differentiation, precursor cells, the
myoblasts, fuse and form long, multinucleated
muscle fibers.
 Myofibrils soon appear in the cytoplasm, and by the
end of the third month, cross-striations typical of
skeletal muscle appear.
 A similar process occurs in the seven somitomeres in
the head region rostral to the occipital somites.
Somitomeres remain loosely organized structures,
however, never segregating into sclerotome and
dermomyotome segments.

11. MOLECULAR REGULATION OF
SKELETAL MUSCLE DEVELOPMENT
 BMP4 and probably FGFs from lateral plate mesoderm, together with
WNT proteins from adjacent ectoderm, signal the dorsolateral cells
of the somite to express the muscle-specific gene MYO-D.
 BMP4 secreted by overlying ectoderm induces production of WNT
proteins by the dorsal neural tube, and these proteins cause
dorsomedial cells of the somite to activate MYF5, another muscle
specific gene.

12. MOLECULAR REGULATION OF
SKELETAL MUSCLE DEVELOPMENT

13. PATTERNING OF MUSCLES
Patterns of muscle formation are controlled
by connective tissue into which myoblasts
migrate.
 In the head region, C.T. are derived from
neural crest cells.
 In cervical and occipital regions, C.T.
differentiate from somitic mesoderm.
 In the body wall and limbs, C.T. originate
from lateral plate mesoderm.

14. DERIVATIVES OF PRECURSOR
MUSCLE CELLS
 By the end of 5th week,
prospective muscle cells are
collected into 2 parts:
 a small dorsal portion, the epimere
(formed from dorsomedial cells of
somite), and
 A large ventral part, the hypomere
(formed from dorsolateral cells of
somite)
 Nerves innervating segmental
muscles are also divided into a
dorsal primary ramus for the
epimere and a ventral primary
ramus for the hypomere.

15.  Myoblasts of the epimeres form the extensor
muscles of the vertebral column, & those of the
hypomeres give rise to muscles of limbs & body
wall;
 Myoblasts from cervical hypomeres form the
scalene, geniohyoid, and prevertebral muscles.
 Myoblasts from the thoracic segments split into
three layers (external, internal, innermost
intercostal)
 Myoblasts of abdominal wall form 3 layers
 Myoblasts from the hypoblast of the lumbar
segments form the quadratus lumborum muscle.
 Myoblasts from sacral and coccygeal regions form
the pelvic diaphragm & striated muscles of the anus.

16.  A ventral longitudinal muscle
column arises at the ventral tip
of the hypomeres.
 This column is represented by
the rectus abdominis muscle
in the abdominal region and
by the infrahyoid
musculature in the cervical
region.
 In the thorax, the longitudinal
muscle normally disappears
but is occasionally represented
by the sternalis muscle.

17. HEAD MUSCULATURE
 All voluntary muscles of the head region are derived from
paraxial mesoderm (somitomeres and somites) including
the:
 Musculature of the tongue,
 Eye (except that of iris which is derived from the optic
cup ectoderm)
 Musculature of pharyngeal arches, innervated by the
pharyngeal arch nerves.
 Pattern of muscle formation in head is directed by C.T
elements derived from neural crest cells.

18. ORIGINS OF CRANIOFACIAL
MUSCLES
MESODERMAL
ORIGIN
MUSCLES INNERVATION
Somitomeres 1 & 2 Superior, medial, ventral
recti
Oculomotor (III)
Somitomere 3 Superior oblique Trochlear (IV)
Somitomere 4 Jaw closing Trigeminal (V)
Somitomere 5 Lateral rectus Abducens (VI)
Somitomere 6 Jaw opening, other 2nd arch Facial (VII)
Somitomere 7 Stylopharyngeus Glossopharyngeal (IX)
Somites 1 & 2 Intrinsic laryngeals Vagus (X)
Somites 2 to 5 Tongue Hypoglossal (XII)

19. LIMB MUSCULATURE
 Ist indication of limb
musculature is observed in
7th week of development as
a condensation of
mesenchyme near the base
of limb buds.
 Mesenchyme is derived
from dorsolateral cells of
somites (C4 to T2) that
migrate into the limb bud to
form the muscles.
Limb buds with their segments of origin
indicated. With further development
the segmental pattern disappears; however, an
orderly sequence in the dermatome
pattern can still be recognized in the adult.

21.  With elongation of the limb buds,
the muscular tissue splits into
flexor and extensor components
 The upper limb buds lie opposite
the lower five cervical and upper
two thoracic segments.
 The lower limb buds lie opposite
the lower four lumbar and upper
two sacral segments.
 As in other regions, connective
tissue dictates the pattern of
muscle formation, and this tissue
is derived from somatic
mesoderm, which also gives rise
to the bones of the limb.
Limb buds at 7 weeks

22. 6 week embryo showing
myotome regions of somites
that give rise to skeletal
muscles
8 week embryo showing the
developing trunk & limb
musculature

23.  As soon as the buds are formed, the appropriate
spinal nerves penetrate into the mesenchyme.
 At first, they enter with isolated dorsal and ventral
branches, but soon these branches unite to form
large dorsal and ventral nerves.
 The radial nerve, which supplies the extensor
musculature, is formed by a combination of the
dorsal segmental branches.
 The ulnar and median nerves, which supply the
flexor musculature, are formed by a combination
of ventral branches.

24.  Immediately after the nerves have entered
the limb buds, they establish an intimate
contact with differentiating mesodermal
condensations.
 The early contact between the nerve and
muscle cells is a pre-requisite for their
complete functional differentiation.
 Spinal nerves not only play an important
role in differentiation and motor innervation
of limb musculature but also provide
sensory innervation for dermatomes.

25. CLINICAL CORRELATES
 Poland anomaly: it
is the total or partial
absence of pectoralis
major muscle.
 Similarly palmaris
longus, serratus
anterior & quadratus
femoris muscles may
be partially or totally
absent.

26. Prune belly syndrome
 Partial or complete
absence of abdominal
musculature
 Usually the abdominal
wall is so thin that organs
are visible and easily
palpated.
 Often associated with
malformations of the
urinary tract and bladder.

27. DEVELOPMENT OF CARDIAC
MUSCLES
 From splanchnic mesoderm surrounding the
endothelial heart tube.
 Myoblasts adhere to one another by special
attachments that later form intercalated discs (but
the intervening cell membranes do not disintegrate).
 Myofibrils develop as in skeletal muscles but
myoblasts do not fuse.
 During later development, few special bundles of
muscle cells with irregularly distributed myofibrils
(future purkinjie fibers) form the conducting system
of heart.

28. DEVELOPMENT OF SMOOTH
MUSCLES
 Smooth muscle for the dorsal aorta and large
arteries is derived from lateral plate mesoderm and
neural crest cells
 In the coronary arteries, smooth muscle originates
from pro-epicardial cells and neural crest cells
(proximal segments).
 Smooth muscle in the wall of gut and gut
derivatives is derived from splanchnic layer of
lateral plate mesoderm

29. DEVELOPMENT OF SMOOTH
MUSCLES (cont’d)
 The musculature of the iris (sphincter and dilator
pupillae) and the myoepithelial cells in the
mammary and sweat glands are thought to be
derived from the mesenchymal cells that originate
from the ectoderm.
 As smooth muscle fibers develop into sheets or
bundles, they receive autonomic innervation.

30. MOLECULAR REGULATION OF SMOOTH
MUSCLE DIFFERENTIATION
 Serum response factor (SRF) is a transcription factor
responsible for smooth muscle cell differentiation. This
factor is upregulated by growth factors through kinase
phosphorylation pathways.
 Myocardin and myocardin-related transcription factors
(MRTFs) then act as co-activators to enhance the activity
of SRF, thereby initiating the genetic cascade responsible
for smooth muscle development.

31. INTEGUMENTARY
SYSTEM

32. The integumentary system consists of:
 The skin
 Appendages of skin
 Sweat glands
 Nails
 Hair
 Sebaceous glands
 Arrector muscles of hairs
 Mammary gland

33. SKIN HAS A TWO-FOLD ORIGIN:
EPIDERMIS: develops from surface ectoderm
DERMIS: develops from underlying mesenchyme
(derived from mesoderm)

34. EPIDERMIS
 Initially, the embryo is
covered by a single layer
of ectodermal cells.
 In the beginning of the
2nd month, this
epithelium divides and
form a layer of squamous
cells, the periderm or
epitrichium, on the
surface.

35.  Continuous keratinization
& desquamation of
periderm cells.
 Continuous replacement
of periderm cells by
underlying basal cells.
 With further proliferation
of cells in the basal layer
(stratum germinativum), a
third intermediate zone is
formed by 11 weeks.

36.  Replacement of periderm
cells continues until about
21st week;
 Thereafter, the periderm
disappears & the stratum
corneum forms.
 Proliferation of cells in
stratum germinativum also
forms epidermal ridges,
which extend into developing
dermis begin to
appear at 10 weeks &
permanently established by
17th week Finger
prints.

37.  The transformation of surface ectoderm into
multilayered epidermis results from continuing
Inductive interactions with the dermis (i.e.
ectodermal / mesenchymal interaction ).

38.  Skin is classified as THICK or THIN SKIN, based
on the thickness of the epidermis.
 Thick skin: palms and soles; lacks hair follicles,
arrector pili muscles, & sebaceous glands BUT has
sweat glands.
 Thin skin: most of the rest of the body; contains hair
follicles, arrector pili muscles, sebaceous & sweat
glands.

39. Vernix caseosa
 Vernix (Latin., varnish)
 White greasy substance that covers the fetal skin.
 Contains
 exfoliated periderm cells
 Sebum
 Protects developing skin from constant exposure to
amniotic fluid (with its urine content)
 Facilitates birth of the fetus, because of slippery
nature.

40. Development of melanocytes
 During the first 3 months of development,
dermis is invaded by neural crest cells.
 These cells differentiate into melanoblasts.
 They then migrate to dermo-epidermal
junction & differentiate into melanocytes (with
formation of pigment granules, at 40-50 days )

41.  The cell bodies of
melanocytes are usually
confined to basal layers of
epidermis; however their
dendritic processes extend
between the epidermal cells.
 melanocyte begin producing
melanin (Gr, melas black )
pigment , before birth which
can be transferred
intercellularly to
keratinocytes of skin & hair
bulb by way of dendritic
processes.

42. Development of melanocytes (cont’d)
 Pigment formation can be observed prenatally
in the epidermis of dark skinned fetuses.
 Increased amounts of melanin are produced in
response to UV light.
 Relative content of melanin in melanocytes
accounts for different colours of skin.

43. PIGMENTARY DISORDERS
 Defects arise because of faulty
migration or proliferation of
neural crest cells. Some types
of WS result from mutations in
PAX3, including WS1 and
WS3
 PIEBALDISM
 rare autosomal dominant disorder of
melanocyte development
 Patchy absence of hair pigment.
 patches of hypopigmentation and
depigmentation on the mid-forehead,
chest, abdomen, and upper and lower
extremities. A white forelock and
pigment loss of the medial eyebrows
 WAARDENBURG-KLEIN
SYNDROME
 a rare genetic disorder most often
characterized by varying degrees of
deafness, minor defects in structures
arising from the neural crest, and
pigmentation anomalies.
 Patches of white hair
 Heterochromia irides
 White patches of skin
 Deafness

44.  ALBINISM
 Autosomal recessive trait
 Disease of melanocyte function
 Characterized by globally reduced or absence of pigmentation in
skin, hair and eyes
 VITILIGO
 Result from loss of melanocytes due to an autoimmune disorder.
 Patchy loss of pigment from effected areas including skin and
overlying hair and oral mucosa
 Associated with other autoimmune diseases, particularly of thyroid
 DERMATOGLYPHICS
 scientific study of fingerprints.
 In humans and animals, dermatoglyphs are present on fingers,
palms, toes, and soles.

45. DERMIS
The dermis is derived from
somatic layer of lateral plate
mesoderm & some from the
dermatomes of the somites
During the 3rd and 4th
months, this tissue, the
corium, form many irregular
papillary structures, the
dermal papillae/ dermal
ridges , which project upward
into the epidermis.

46.  Most of these papillae usually contain a
small capillary (providing nourishment to
epidermis) or sensory nerve end organ.
 The deeper layer of the dermis, the
subcorium, contains large amounts of fatty
tissue.

47. KERATINIZATION OF SKIN
ICHTHYOSIS
 It is excessive keratinization of
the skin
 is characteristic of a group of
hereditary disorders that are
usually inherited as autosomal
recessive trait but may also be
X-linked.

48. ICHTHYOSIS

49. HAIR
 Hairs appear as solid
epidermal proliferations
penetrating the underlying
dermis.
 At their terminal ends, hair
buds invaginate.
 The invaginations, hair
papillae are rapidly filled with
mesoderm in which vessels
and nerve endings develop.

50.  Soon, cells in the center of the
hair buds become spindle
shaped and keratinized forming
the hair shaft, while peripheral
cells become cuboidal giving
rise to the epithelial hair
sheath.
 The dermal root sheath is
formed by the surrounding
mesenchyme.
 A small smooth muscle attaches
to the dermal root sheath. This
muscle is known as an arrector
pili muscle (derived from
mesenchyme).

51.  Contraction of arrector pili muscles cause
‘goose bumps’ on the surface of the skin.
 The hair forming the eyebrows and the cilia
forming the eyelashes have no arrector pili
muscles.

52.  Continuous proliferation of
epithelial cells at the base of the
shaft pushes the hair upward.
 By the end of 3rd month, the
first hair appear on the surface, in
the region of the eye brow and
upper lip.
 The first hair that appears, lanugo
hair, is shed at about the time of
the birth and is later replaced by
coarser hairs arising from new
hair follicles.

53. ABNORMALITIES OF HAIR
DISTRIBUTION
 HYPERTRICHOSIS
Excessive hairiness is
caused by unusual
abundance of hair
follicles

54.  ATRICHIA
It is the congenital absence of hair and
is usually associated with abnormalities
of other ectodermal derivatives such as
teeth and nails.

55. DEVELOPMENT OF SEBACEOUS
GLANDS
 Epithelial wall of hair follicle
usually show a small bud
penetrating surrounding
mesoderm. The buds branch to
form alveoli & associated ducts.
 Central cells of alveoli break
down, forming oily secretion –
sebum, that is released on hair
shaft & passed to the skin
surface, where it mixes with
desquamated peridermal cells to
form vernix caseosa.
 Sebaceous glands independent of
hair follicles (glans penis, labia
minora) develop in a similar
manner, to bud from the
epidermis.

57. DEVELOPMENT OF ECCRINE
SWEAT GLANDS
 As epidermal downgrowths into
underlying mesenchyme
 Its end coils – primordium of
the secretory part.
 Epithelial attachment to
epidermis – primordium of the
duct
 Central cells of primordial ducts
degenerate, forming a lumen.
 The peripheral cells of secretory
part differentiate into
myoepithelial & secretory cells.
 Eccrine sweat glands begin to
function shortly after birth.

58. DEVELOPMENT OF APOCRINE
SWEAT GLANDS
 Confined mostly to axilla, pubic, perineal
regions.
 Develops from downgrowths of the stratum
germinativum of the epidermis that gives rise
to hair follicles.
 As a result, the ducts of these glands open not
onto the skin surface but into the upper part of
hair follicles , superficial to the openings of
sebaceous glands.
 They secrete only after puberty.

59. DEVELOPMENT OF NAILS
 Toenails and fingernails begin to develop at
the tips of the digits at about 10 weeks.
 Development of fingernails precedes that of
toenails by about 4 weeks.

60.  The primordia of nails appear as thickened areas of
epidermis at the tip of each digit.
 Later these nail fields migrate onto the dorsal surface
carrying their innervation from the ventral surface.
 The nail fields are surrounded laterally and
proximally by folds of epidermis, the nail folds.
 Cells from the proximal nail fold grow over the nail
field and become keratinized to form the nail plate.

61.  At first the developing nail is covered by
superficial layers of epidermis, the
eponychium.
 This later degenerates exposing the nail except
at its base where it persists as the cuticle.
 The fingernails reach the fingertips by about
32 weeks; the toenails reach the toetips by
about 36 weeks.

62.  CONGENITAL ANONYCHIA
 Absence of nails at birth – very rare
 Anonychia results from failure of the nail folds to
form or from failure of the proximal nail folds to
form nail plates.

63. MAMMARY GLANDS
 First indication of mammary
glands is found in the form of a
band like thickening of
epidermis, the mammary line or
mammary ridge
 In a seven week embryo---extent
of line—base of forelimb to
hindlimb.
 Major part of the mammary line
disappears; a small portion in the
thoracic region persists and
penetrates the underlying
mesenchyme.

64. Here, it forms 16 – 24 sprouts
which in turn give rise to small
solid buds.
By the end of the prenatal life, the
epithelial sprouts are canalized and
form the lactiferous ducts,
whereas the buds form small ducts
and alveoli of the gland.
Initially, the lactiferous ducts open
into a small epithelial pit
Shortly after birth, this pit is
transformed into the nipple by
proliferation of the underlying
mesenchyme.

66. MAMMARY GLAND
ABNORMALITIES
Polythelia—
accessory nipples.
Usually in axillary
region

67. Polymastia– remnant of mammary line
develops into complete breast
Inverted nipple – the lactiferous ducts
open into the original epithelial pit that
has failed to evert, due to failure of
underlying mesenchymal proliferation.