Sukumal Chongthammakun,Ph.D. Department of Anatomy Faculty of Science, Mahidol University

Germ layer contribution

Chondrogenesis Begins week 5 Condensation and differentiation Centers of chondrification Secretion of the extracellular matrix Entrapment of chondroblast Formation of chondrocyte

Interstitial growth Appositional growth Growth of cartilage

Osteogenesis Mechanism of bone formation Endochondral ossification Intramembranous ossification

Endochondral ossification Ossification begins at the start of fetal period (mo. 3) Perichondrium differentiates into a layer of osteoprogenitor cells Differentiation into osteoblasts and secretion of a layer of osteoid Calcification and forming a bony collar In the center, cells of the cartilage hypertrophy and degenerate Penetration by the vascular bud

Intramembranous ossification Condensations of mesenchymal cells Secretion of osteoid Spicules are formed Networks of trabeculae Entrapment of osteocytes

The Axial Skeleton 1. The vertebral column 2. The attached rib 3. The sternum 4. The skull

Vertebrae and ribs are formed by endochondral ossification of the sclerotome regions of somites Sclerotome cells surround the developing neural tube Ventral portion forms body(centrum) around the notochord Dorsal portion forms costal processes laterally (T1-12 : articulate with ribs) Intervertebral disks are formed Notochord remains as the nucleus pulposus The fibrocartilage is formed around N. pulposus (Annulus fibrosus)

All somites contribute to the formation of the axial skeleton of the body and head 42 to 44 pairs of somites develop 4 occipital (1 degenerates) 8 cervical 12 thoracic 5 lumbar 5 sacral 8-10 coccygeal (last 5-7 degenerate)

Development of the skull Neurocranium membranous neurocranium cartilaginous neurocranium Viscerocranium membranous viscerocranium cartilaginous viscerocranium

Membranous Neurocranium

Cartilaginous Neurocranium

Membranous Viscerocranium

Cartilaginous Viscerocranium

Somatic lateral plate mesoderm forms the skeleton of the appendages : the limb bones and appendicular girdles The appendicular skeleton is formed by endochondral ossification of cartilage models Appendicular Skeleton

Development of the Joints Synovial Joints interzonal mesenchyme differenciates : 1. Peripherally: to capsular and other ligaments 2. Centrally: disappears and becomes the joint cavity 3. Where it lines the capsule and articular surfaces: forms the synovial membrane

Development of the Joints Cartilaginous Joints Interzonal mesenchyme differenciates into: Hyaline cartilage eg. Costochondral joints Fibrocartilage eg. Symphysis pubis

Development of Joints Fibrous Joints Interzonal mesenchyme differenciates into: Dense fibrous connective tissue eg. Sutures of the skull

Limbs form by “budding” out from the ventrolateral body surface. Limbs are formed by ectoderm covering a solid mesoderm core, with no endoderm contributions. There is no coelom. Embryonic features unique to the limbs

1. Somatic lateral plate mesoderm: cartilage, bone & CNT 2. Skeletal muscle is outsider migrating in from the somites. 3. Surface ectoderm: epidermis of skin & its specialization 4. Nerves & blood vessels grow in from the body using connective as a guide. Germ layer origins of the limbs

1. Limb mesoderm induces surface ectoderm to form “apical ectodermal ridge (AER)”. 2. AER induces mesoderm underneath to continue proliferation then commit to specific derivatives. 3. Limb mesoderm also induces the formation of limb- specific mesoderm specializations eg. Nails. Limb mesoderm and surface ectoderm interaction

Directed by AER The first deposit is programmed to form humerus The last deposit is programmed to form the bones of phalanges Proximal-Distal Limb Axis

Dorsal side is continuous with the dorsal side surface of the body. Ventral side is continuous with the ventral side surface of the body. Dorsal-Ventral Limb Axis

is established by a gradient of inducing signals released from cells of the “zone of polarizing activity (ZPA)” The most caudal bones (eg. Little finger) form in response to exposure to a maximum of inducer. The most cranial bones (eg. Thumb) form in response to exposure to the lowest concentration of inducer. Retinoic acid may be the ZPA inducer Cranial-Caudal Limb Axis

Limb buds appear at the end of week 4 and the beginning of week 5 and become externally constricted into regions by week 8 Week 6 : Formation of the hands and footplates (circumferential constriction) Week 7-8 : Formation of finger and toe rays (longitudinal constriction) Week 8 : Formation of 2nd circumferential constriction Constriction and Regression

Final feature of limb development : Limbs rotate about their long axis. The arms rotate 90 o dorsolaterally The legs rotate 90 o ventrolaterally Rotation Rotation of the limbs results in : 1. The final orientation of the joints 2. The final location of muscle groups. 3. The mature patterns of sensory innervation of the skin called “dermatome”.

Germ layer origins : All skeletal muscle is derived from somitic myotomes Connective tissue directs muscle mass formation Formation of multinucleated skeletal muscle cells occurs by fusion of myoblasts with each other. Skeletal muscle cell fusion, formation of contractile machinery, and specific fiber types do not require nerve input. Histogenesis of skeletal muscle

Distiguishing between trunk, head and limb muscles 1. Trunk muscles form directly from myoblasts remaining in the myotomes. 2. The cells that migrate form intrinsic limb muscles, and the muscles of shoulder and pelvic girdles. 3. Cells from the most cranial myotomes form head and neck muscle after they migrtae into the pharyngeal arches.

Innervation : the key to the origin of skeletal muscles Cranial nerves : muscles of pharyngeal arches Spinal nerves : muscles of neck, body and limbs Dorsal primary rami Ventral primary rami

Axial muscles of the trunk Trunk (axial) muscles form directly from myotomes. Dorsal portion : epimere epaxial muscles Ventral portion : hypomere hypaxial muscles

Appendage muscles: limbs and appendicular girdles Limb muscles and appendicular girdle muscles all originate from myotomal cells that migrate into the limbs. Dorsal limb bud mases extensors supinators abductors Ventral limb bud masses flexors pronators adductors

The intrinsic limb muscles are formed from both limb muscle masses. All muscles of the appendicular girdles are derived from the dorsal limb muscle mass. Innervation: Dorsal muscle mass : dorsal branches of ventral 1 o rami Ventral muscle mass : ventral branches of ventral 1 o rami Appendage muscles: limbs and appendicular girdles

Muscles of the head and neck Precursors migrate into pharyngeal arches before forming muscles. Innervation helps distinguish the origins.

Origins of the Craniofacial Muscles Mesodermal OriginMusclesInnervation Somitomeres 1, 2Superior, medial, and ventral recti Oculomotor (III) Somitomere 3Superior oblique Trochlear (IV) Somitomere 4Jaw-closing muscles Trigeminal (V) Somitomere 5Lateral rectus Abducens (VI) Somitomere 6Jaw-opening and other 2nd arch musclesFacial (VII) Somitomere 7Stylopharyngeus Glossopharyngeal (IX) Somites 1, 2Intrinsic laryngeals Vagus (X) Somites 2-5Tongue muscles Hypoglossal (XII)

Congenital Defects of the Skull Caused by genetic and environmental factors and disturbing neural crest migration into/and proliferation in pharyngeal arches Anencephaly : failure of cranial neuropore to close in week 4. Craniofacial synostosis : premature closure of sutures between flat bones of neurocranium coronal suture : oxycephaly/turricephaly sagittal suture: scaphocephaly Craniofacial dysostosis : underdevelopment of arch facial bones, including maxill and mandible

Scaphocephaly A. Oxycephaly B. Plagiocephaly

Congenital Defects of Vertebrae and Ribs Hemivertebra : results in scoliosis Spina bifida : vertebral arches fail to fuse dorsally

Congenital Defects of the Limbs Causes : genetic/environment Hyperthermia Drugs eg. Aspirin, anticonvulsant dimethadione, excess RA Achondroplasia (chondrodystrophy) : premature ossification in epiphyseal plate of long bones a. Short vertebral column b. Short limbs with thick diaphyses in long bones c. Sunken midfacial region d. Normal to superior mental capacity

Achondroplasia

Congenital Defects of the Limbs Amelia : complete absence of limb(s) Meromelia : absence of segment(s) of limb(s) Phocomelia : a form of meromelia in which proximal structures are small or absent Polydactyly : extra digits (incomplete and useless) Syndactyly : fused or web digits (lobster claw)

A. Unilateral amelia B. Meromelia A. Syndactyly B. Lobster claw

Congenital Defects of the Skeletal Muscles Muscular dystrophy : a family of genetic diseases in which there is postnatal degeneration of various muscle groups Duchenne muscular dystrophy : caused by a lack of actin- binding protein called dystrophin Absent or underdeveloped muscle groups : associated with bone defects unassociated with bone defects