Developmental Anatomy for DT

(ANA 222; 1/2013)

Musculoskeletal and Integumentary Systems

Objectives: To describe
1. 2. 3. 4. the developments of the axial and appendicular skeletons and joints the developments of the skeletal, cardiac and smooth muscles the developments of the skin and its appendages Some clinical correlations

Dr.Ronnarong Palasoon: Anatomy Unit, Faculty of Science, Rangsit University

The Skeletal System

The Regulation of Somite Differentiation

Sonic hedgehog and noggin cause the ventral part of the somite to form sclerotome and to express PAX1. PAX1 controls chondrogenesis and vertebrae formation. PAX3 demarcates the dermomyotome. WNT proteins activate PAX3 and direct the dorsomedial portion of the somite to differentiate into muscle precursor cells. Neurotrophin 3 directs the middorsal portion of the somite. The activating WNT proteins and inhibitory BMP4 protein influence the dorsolateral portion of the somite to the other muscle precursor cells.

The Development of Skeletal System

1. Paraxial mesoderm - vertebrae and ribs - some bones of skull base 2. Lateral plate (parietal layer) mesoderm - pelvic and shoulder girdles, limbs and sternum 3. Neural crest in the head - skull : cranial vault, face

Phases of Chondrogenesis and Its Regulation Pathways

Skull

Development of the Cranium

At 6 weeks

At 7 weeks

At 12 weeks

At 20 weeks

Skull
NEUROCRANIUM
Chondrocranium Occipital Sphenoid Ethmoid Petrous and mastoid part of temporal Membranous Neurocranium Interparietal part of occipital Parietal Frontal Squamous part of temporal

Skull
VISCEROCRANIUM Cartilaginous Viscerocranium
Pharyngeal Arch I Meckel's cartilage Malleus Incus Pharyngeal Arch II Reichert's cartilage Stapes Styloid process

Membranous Viscerocranium
Maxillary process (superficial) Squamous part of temporal Zygomatic Maxillary Premaxillary Nasal? Lacrimal? Maxillary process (deep) Palatine Vomer Pterygoid laminae Mandibular process Mandible Tympanic ring

Skull of Newborn

sultures

fontanelles

molding

Craniosynostosis
premature closure of one or more sultures

scaphocephaly
- the sagittal suture

brachycephaly
- the coronal sulture

plagiocephaly
-the coronal and lambdoid sutures on one side of the skull

Cranioschisis
the cranial vault fails to form failure of the cranial neuropore to close

anencephaly

meningocele

Vertebra

Vertebral column

Vertebral column
sclerotome: - notochord, neural tube, and the body wall - paired condensation
- loosely arranged cells, cranially - densely packed cells, caudally

resegmentation: - the caudal half of each

sclerotome grows into and fuses with the cephalic half of each subjacent sclerotome

HOX genes Formations: - centrum - neural arch - nucleus pulposus - costal processes

Vertebral Development

5th week

6th week

7th week

At birth

Developments of Ribs and Sternum

Ribs
the costal processes of thoracic vertebrae

Sternum
the parietal layer of lateral plate mesoderm two sternal bands on either side of the midline cartilaginous models of the manubrium, sternebrae, and xiphoid process

Vertebral and Rib Abnormalities

Anatomy of the Muscular System

1. The axial muscles
Muscles of head
- Muscles of facial expression - Muscles of mastication

Muscles of the neck and throat Back muscles Thorax muscles Abdominal wall muscles Muscles of pelvic floor

2. The appendicular muscles

Muscles of upper limbs Muscles of lower limbs

The Development of Muscular System

The muscular system develops from the mesodermal germ layer. Skeletal muscle is derived from paraxial mesoderm forming somites from the occipital to the sacral regions and somitomeres in the head. Smooth muscle differentiates from visceral splanchnic mesoderm surrounding the gut and its derivatives and from ectoderm (pupillary, mammary gland, and sweat gland muscles). Cardiac muscle is derived from visceral splanchnic mesoderm surrounding the heart tube.
Myoblasts (embryonic muscle cells) are derived from mesenchyme . MyoD, a member of the family of myogenic regulatory factors, activates transcription of muscle-specific genes and is considered an important regulatory gene for the induction of myogenic differentiation.

The development of skeletal muscle

Myogenesis (muscle formation) the elongation of the nuclei and cell bodies of mesenchymal cells

Myoblasts (MyoD, myogenin, Myf-5, and myogenic regulatory factor 4)

Myotubes: elongated, multinucleated, cylindrical structures Signaling molecules : regulate the beginning of myogenesis and the induction
of the myotome . - Shh, from the ventral neural tube and notochord - Wnts, BMP-4,from the dorsal neural tube - Wnts, BMP-4, overlying ectoderm

The development of skeletal muscle

Myotome:
epaxial division (Myf-5) hypaxial division (MyoD)

The development of cardiac muscle

Primordial myocardium Cardiac myoblasts Heart muscle
(the fourth week)

Purkinje fiber (late embryonic period)

The development of smooth muscle

spindle-shaped myoblasts (with elongated nuclei)

Mesenchyme

Smooth muscle
dorsal aorta and large arteries coronary arteries wall of the gut and gut derivatives sphincter and dilator muscles of the pupil and muscle tissue in the mammary and sweat glands

lateral plate mesoderm and neural crest cells proepicardial cells and neural crest cells (proximal segments) splanchnic layer of lateral plate mesoderm

ectoderm

Embryological Origins of the Major Classes of Muscle

Embryological Origin
Somitomeres 1 through 3 and prechordal plate Somitomere 4 Somitomere 5 Somitomere 6 Somitomere 7 Somites 1 and 2 Occipital somites (1 through 7) Trunk somites Splanchnic mesoderm Splanchnic mesoderm Local mesenchyme

Derived Muscle
Most extrinsic eye muscles

Innervation
Cranial nerves III and IV

Jaw-closing muscles Lateral rectus muscle of eye Jaw-opening and other secondarch muscles Third-arch branchial muscles Intrinsic laryngeal muscles and pharyngeal muscles Muscles of tongue, larynx, and neck Trunk muscles, diaphragm, and limb muscles Cardiac muscle Smooth muscles of gut and respiratory tract Other smooth muscle: vascular, arrector pili muscles

Cranial nerve V (mandibular branch) Cranial nerve VI Cranial nerve VII Cranial nerve IX Cranial nerve X Cranial nerves XI and XII, cranial cervical nerves Spinal nerves Autonomic Autonomic Autonomic

From Carlson BM: Patten's foundations of embryology, ed 6, New York, 1996, McGraw-Hill.

Anomalies of Muscles

Poland syndrome:
Absence of the pectoralis major, often its sternal part, is usually associated with syndactyly (fusion of digits).

Prune belly syndrome:

Partial or complete absence of abdominal m.

Anomalies of Muscles

Congenital Torticollis

Arthrogryposis
(congenital joint contractures)

Development of the limb buds

5th week

6th week

8th week

Limb bud: mesenchyme core covered by ectoderm The forelimb appears first followed by the hindlimb 1 to 2 days later. Apical ectodermal ridge (AER): thick ectoderm at the distal border of the
limb exerts an inductive influence on adjacent mesenchyme

progress zone

Development of the limb buds

Development of the limb buds

Days: 27 32 41 46 50 52

Days:

28

36

46

49

52

56

Development of the limbs

The rotation of limbs

The fifth week of gestation: the limbs extending ventrally the hand- and footplates facing each other
48 days 51 days

The seventh week of gestation: the upper limb rotating 90 laterally the lower limb rotating approximately 90 medially

54 days

56 days

Cartilage and Bone of Limbs The 6th week: hyaline cartilage models The 12th week: primary ossification center endochondral ossification diaphysis At birth: completed ossification of diaphysis secondary ossification center epihysis

Regulation of Limb Patterning and Growth

Limb outgrowth: - lateral plate mesoderm cells - TBX5 and FGF10 (forelimb) - TBX4 and FGF10 (hindlimb)

Patterning of proximodistal axis

BMPs (bone morphogenetic proteins) induce formation of the AER. Radical fringe restricts the location of the AER to the distal tip of the limbs. SER2 is expressing at the AER (apical ectodermal ridge). Engrailed-1 represses expression of Radical fringe. The ridge expresses FGF4 and FGF8, which maintain the progress zone.

Regulation of Limb Patterning and Growth

Patterning of anteroposteroir axis
The zone of polarizing activity (ZPA): a cluster of cells at the posterior border of the limb. The cells in ZPA produce retinoic acid (vitamin A). RA initiates expression of sonic hedgehog (SHH) regulating the anteroposterior axis.

Patterning of dorsoventral axis

BMPs in the ventral ectoderm induce expression of EN1. EN1 represses WNT7a expression, restricting it to the dorsal limb ectoderm. WNT7a induces expression of LMX1 specifing cells to be dorsal. In addition, WNT7a maintains SHH expression in the ZPA and therefore indirectly affects anteroposterior patterning as well.

Regulation of Limb Patterning and Growth

Bone type and shape are regulated by HOX genes, whose expression is determined by the combinatorial expression of SHH, FGFs, and WNT7a. HOXA and HOXD clusters are the primary determinants of bone morphology.

Types of Joint

Joint Formations
Joints are formed in the cartilaginous condensations. A joint interzone is induced when chondrogenesis is arrested. A joint cavity is formed by cell death. Surrounding cells differentiate into a joint capsule. WNT14 appears to be the inductive signal regulating the positioning of joints. synovial, cartilaginous, and fibrous joints

Limb Anomalies

amelia: complete absence of limb meromelia: partial absence of limb

Digital Anomalies

A.Brachydactyly, short digits. B. Syndactyly, fused digits. C. Polydactyly, extra digits. D. Cleft foot, lobster claw deformity.

Bilateral talipes equinovarus (clubfeet)

The development of the Integumentary System

the skin and its appendages: sweat glands, nails, hairs, sebaceous glands, and arrector muscles of hairs the mammary glands and teeth

Development of skin and skin appendages SKIN

(a) A superficial layer, the epidermis, develops from the surface ectoderm. (b) A deep layer, the dermis, develops from the underlying mesenchyme.

Epidermis
5 weeks

layer of surface ectodermal cells:

primordium of epidermis

7 weeks

the periderm a basal (germinative) layer

periderm continually undergo keratinization and desquamation and are replaced by cells arising from the basal layer.

11 weeks

vernix caseosa:
the white greasy substance protects the developing skin facilitates birth of the fetus.

At 10 weeks: epidermal ridges Late embryonic period: melanoblasts

(neural crest cells)

melanocytes

Dermis
- three sources:
(a) lateral plate mesoderm: dermis in the limbs and body wall (b) paraxial mesoderm: dermis in the back (c) neural crest cells: dermis in the face and neck.

During the third and fourth months: dermal papillae Sweat Glands
two types : eccrine and apocrine

Eccrine sweat glands

- skin throughout most of the body
- function shortly after birth

Apocrine sweat glands

- axilla, pubic, and perineal regions and areolae of the nipples - develop during puberty - arise from the same epidermal buds that produce hair follicles

Development of Hairs and Sebaceous glands

At 9-12 weeks: hair buds hair bulbs germinal matrix epithelial root sheaths sebaceous glands hair papillae epithelial root sheaths arrector muscles of hairs melanoblasts

Mammary Glands

Mammary Glands
a modified and highly specialized type of sweat glands. Mammary buds: solid downgrowths of the epidermis into the underlying mesenchymethe , at sixth week , responding to an inductive influence from the mesenchyme. mammary crests: thickened strips of ectoderm extending from the axillary to the inguinal regions, appeared during the fourth week Canalization of these buds: induced by placental sex hormones and continued until late gestation, and by term lactiferous ducts and their branches The fibrous connective tissue and fat: the surrounding mesenchyme mammary pit : the late fetal period

Clinical correlations
Hypertrichosis Hyperpigmentation Ichthyosis Angiomas Albinism Supernumerary Breasts
- extra breast (polymastia) - nipple (polythelia)

Development of Nails

Toenails and fingernails begin to develop at the tips of the digits at about 10 weeks. nail fields: the primordia of nails, thickened areas of epidermis at the tip of each digit nail folds: surrounded nail fields laterally and proximally nail plate: cells from the proximal nail fold growing over the nail field and keratinizing eponychium (cuticle): a narrow band of epidermis Hyponychium: the skin under the free margin of the nail The fingernails reach the fingertips by approximately 32 weeks the toenails reach the toetips by approximately 36 weeks.

Development of Teeth
Two sets of teeth : deciduous and permanent teeth. Teeth develop from oral ectoderm, mesenchyme, and neural crest cells.

Bud stage 8 weeks

Cap stage 10 weeks

Bell stage 3 months 6 months

Development of Teeth
dental lamina: the basal layer of the epithelial lining of the oral cavity forms a C-shaped structure, at the sixth week dental buds cap stage: invagination of the buds into the deep surface - a cap an outer layer, the outer dental epithelium - an inner layer, the inner dental epithelium - a central core of loosely woven tissue, the stellate reticulum. dental papilla: the mesenchyme originating in the neural crest bell stage: the dental cap grows and the indentation deepens - odontoblasts: producing dentin - the pulp of the tooth - ameloblasts: epithelial cells of the inner dental epithelium enamel knot regulating early tooth development

Development of Teeth
epithelial root sheath: the dental epithelial layers penetrating into the underlying mesenchyme, formation of the root of the tooth cementoblasts: mesenchymal cells on the outside of the tooth and in contact with dentin of the root, producing the cementum periodontal ligament: mesenchyme outside the cement layer The eruption of deciduous or milk teeth occurs 6 to 24 months after birth.

The tooth just before birth

The tooth just after eruption

Anomalies of teeth

enamel hypoplasia: defective enamel formation causes pits and/or fissures in the enamel of teeth variations of tooth shape: abnormally shaped teeth enamel pearls: spherical masses of enamel on the root of a tooth numerical abnormalities: supernumerary teeth, anodontia, gemination Amelogenesis imperfecta: a complex group of at least 14 different clinical entities that involve developmental aberrations in enamel formation in the absence of any systemic disorder