XY2141. Embryology. Development of Musculoskeletal System 2024 PDF

XY2141. Embryology. Development of musculoskeletal system Dr Viktoriia Yerokhina, Lecturer in Medical Sciences [email protected]  EMBR.06 - Development of musculoskeletal system EMBR.06.05 - Describe the organization of the somite's EMBR.06.06 - Desc...

XY2141. Embryology. Development of musculoskeletal system Dr Viktoriia Yerokhina, Lecturer in Medical Sciences [email protected]  EMBR.06 - Development of musculoskeletal system EMBR.06.05 - Describe the organization of the somite's EMBR.06.06 - Describe the development of the axial skeleton Learning EMBR.06.07 - Describe the development of the appendicular skeleton outcomes EMBR.06.08 - Describe the development of skeletal muscle in the head, torso and limbs EMBR.06.09 - Describe the development components of the limb EMBR.06.10 - Describe the development of the proximal- distal, medial-lateral anterior-posterior surfaces of the limb EMBR.06.11 - Describe the development of the arterial perfusion of the limb buds EMBR.06.12 - Describe the development of cardiac and smooth muscles. 2 Mesoderm Intraembryonic mesoderm divides into: Paraxial (somites), Intermediate (nephrotome) Lateral plate mesoderm. Paraxial mesoderm extends as a longitudinal column on either side of the notochord and the developing neural tube. 3 Paraxial mesoderm Developing otic capsules (neuroectodermal thickenings that form the membranous labyrinth of internal ear) divide the paraxial mesoderm into: Preotic part is the unsegmented head mesoderm (somitomeres). Postotic part shows 40-45 pairs of segments called somites that appear in craniocaudal sequence. 4  Somites Appear between the 20th and 30th day of development → 4th week is known as somite period of development. A human has around 40-45 pairs of the somite. A cross section through a somite shows that it is a triangular structure and has a cavity. 5 Somites 6 Somites subdivision 1. Sclerotome - ventromedial part; cell migrate medially, surround the neural tube and give rise to the vertebral column and ribs. 2. Dermatome - lateral part; cells migrate, line the deep surface of the ectoderm; give rise to some dermis and to subcutaneous tissue. 3. Myotome - intermediate part; gives rise to striated muscle. *Recently, it has been held that the dermatome only forms dermis on the back of the head and trunk, and that dermis elsewhere is derived from lateral plate mesoderm. 7  Somites In the cervical, thoracic, lumbar and sacral regions, one spinal nerve innervates each myotome (number of somites formed in these regions corresponds to the number of spinal nerves). In the coccygeal region, the somites exceed the number of spinal nerves but many of them subsequently degenerate. 8 Distribution of somites and their skeletal and muscular derivatives The first cervical is not the most cranial somite to be formed. Cranial to cervical somite, there are: o Occipital somites (4–5) which give rise to muscles of the tongue and base of the skull. o Preoccipital (or preotic) somites give rise to extraocular muscles of the eyeball and base of the skull. 9 Which part of the somite gives rise to vertebral column and ribs? A. Dermatome B. Myotome C. Sclerotome 10 General development of bones Most of the bones are of mesodermal origin. Depending on the mode of ossification bones can be classified as: cartilaginous bones (mesenchyme → cartilage → bone), membranous bones (mesenchyme → bone) membrano-cartilaginous bones (mixed) Clavicle is the first bone in the body to ossify. Most bones of the axial skeleton are derived from sclerotomes of somites and head mesoderm. Bones of the shoulder, hip girdle, limbs, arise from somatopleuric layer of lateral plate mesoderm. Some bones of the face and skull are derivatives of the mesoderm of pharyngeal arches that are invaded by neural crest. 11 Stages of ossification of a typical long bone 12 Development of axial skeleton Axial skeleton consists of: vertebral column, ribs, sternum, skull (discussed in the previous semester). Development of the vertebral column: It develops from sclerotomes of somites. Cells of each sclerotome get converted into loose mesenchyme, Mesenchyme migrates medially and surrounds the notochord. 13 Development of the vertebral column Includes 3 stages: precartilage stage, chondrification state, ossification state. 14 Development of the vertebral column I. Precartilage stage Cells of sclerotome migrate in three directions: 1. Ventromedial group a. Densely arranged cells form intervertebral disc b. Loosely arranged cells fuse with the cells of underlying sclerotome to form centrum (body of vertebra) → body of each vertebra develops from 2 adjacent sclerotomes. 2. Dorsal group covers the neural tube and form vertebral arch and spine of vertebrae. 3. Venterolateral group forms costal elements. 15 Development of the vertebral column II. Chondrification stage During the 6th week of IUL, chondrification of mesenchymal vertebrae begins. III. Ossification stage Begins in IUL and continues up to 25 years of age. 3 primary centres: 1 for centrum, 1 for each half of the vertebral arch. At birth, each vertebra has 3 parts (body and two halves of vertebral arch) connected by cartilages. 3–6 years: 3 parts fuse with each other Vertebral arch (neural arch) of developing vertebra forms pedicel, laminae, spine and articular processes. 16 Postnatal vertebra Development of the vertebral column Secondary centres: total 5 centres: 1 for tip of each transverse process, 1 for tip of spinous process 1 for upper and 1 for lower surface of body of vertebra 25 years: all secondary centres fuses with rest of the vertebra. 17 Development of the vertebral column 18 Resegmentation of sclerotomes Each sclerotome is divided into cranial and caudal portions by a transverse line called intrasegmental boundary or von Ebner’s fissure. Caudal dense segment of each sclerotome fuses with the cranial loose segment of the sclerotome caudal to it, with each of the two segments of the sclerotome contributing to a vertebra. This process is called resegmentation of the sclerotomes. Vertebrae are intersegmental in development. 19 Resegmentation of sclerotomes 20 Flowchart: development of vertebra 21 Formation of intervertebral disc Notochordal cells form a gelatinous core called nucleus pulposus. Annulus fibrosus develops from sclerotomal cells. 22  Development of ribs Develop from costal processes in the thoracic region. Costal processes at first elongate to form cartilaginous costal arches, which are then ossified to form the ribs. In cervical, lumbar, and sacral regions, the costal processes remain rudimentary and are represented by a small part of the transverse process of each vertebra called costal element. Mesenchyme near the junction of transverse process and costal arch undergo differentiation to form costotransverse joint. 23 Development of ribs 24 Derivatives of costal element Derivatives of costal element In cervical region: anterior root, anterior tubercle, costotransverse bar and posterior tubercle In thoracic region: rib In lumbar region: transverse process In sacral region: anterior 2/3rd of lateral mass. 25  Development of sternum Sternum develops from mesodermal condensation (lateral plate mesoderm) in the anterior body wall. 3 Stages of development: 1. Formation of mesenchymal sternal bars: in midline, the lateral plate mesoderm of anterior body wall forms 2 mesenchymal sternal bars that undergo chondrification and develop cartilaginous sternal bars. 2. Formation of cartilaginous sternum model: 2 cartilaginous sternal bars fuse in the midline to form cartilaginous sternum model that has manubrium, body and xiphoid process. 26  Development of sternum 3. Ossification of sternum Ossification centres for sternum appear before birth except for the xiphoid (occurs in childhood). For manubrium: a pair of ossification centres appears in 5th month of IUL For body: 4 pairs of ossification centres appear in 6th, 7th, 8th, 9th month of IUL (from above downwards). Each pair of centres fuses to form sternebrae. Fusion of four sternebrae takes place from below upward and completes by 25 years of age. For xiphoid process: centre appears in 3rd year of life and fuses with body by 40 years. 27 What is the derivative of the notochord? A. Annulus fibrosus B. Body of the vertebra C. Nucleus pulposus D. Ribs and sternum E. Laminae and pedicles of the vertebra F. Muscles that cover the vertebral column 28 Which order would correctly describe the process of the sternum formation? A. Ossification, mesenchyme formation, formation of cartilage model B. Formation of mesenchymal sternal bars, formation of cartilage sternal bar model, ossification C. Formation of cartilage sternal bar model, formation of mesenchymal sternal bar model, ossification 29 Development of limbs Limbs develop from mesenchyme of limb buds. Limb buds appear as outpouchings from the ventrolateral aspects of the body wall at the end of the 4th week of IUL. Forelimbs appear first followed by hindlimbs 1 or 2 days later. 30 Development of limbs 1. Formation of limb bud primordia (end of 4th week) 2. Formation of limb bud (2nd month, limb primordia enlarge) * Forelimb bud grows faster than lower limb buds 3. Formation of limbs. 31 Development of limbs 3. Formation of limbs Ectoderm at the tip of the limb bud thickens to form apical ectodermal ridge (AER). 6th week of IUL: terminal part of the limb bud becomes flattened to form hand and foot plates and are separated from the rest of the limb bud by a circular constriction. The expanded plate exhibits five longitudinal mesodermal condensations or digital rays. 32  AER Apical ectodermal ridge – present until the finger origin - inductor of limb development. AER secretes growth factor, which initiates outgrowth of the limb mesenchyme that initiates formation of the limb bud. 33 Development of limbs Later second constriction divides the rest of the limb bud into two segments. Now main parts of the limb become recognizable (e.g., arm, forearm, and hand in upper limb; and thigh, leg, and foot in lower limb). Now the digits are formed in the hand and foot plates following cell death in the ectodermal ridges. 34  Sequence of limb bud development in human embryos A. Upper limb bud appearing. B. All four limb buds visible; upper limb bud more protuberant than lower limb bud. C. Upper limb bud elongated and tapered; lower limb bud enlarging. D. Handplate rounded without digital rays, lower limb bud elongated without distinct footplate. E. Handplate has visible digital rays; footplate has rounded configuration. F. Handplate notched along the rim, rays readily discernible, elbow usually seen, early toe rays may be seen. G. Toe rays are more prominent but lack interdigital notches along the rim of the footplate. 35 ahead H. Enlarged view at stage showing definition of digital rays and digital separation of fingers. As in all stages, hand development is about 2 days of foot development.  Rotation of limbs Initially, the limb buds are paddle shaped and each bud has preaxial and postaxial border. Digit formed along the preaxial border is thumb in the upper limb and great toe in the lower limb. Limbs now rotate: Upper limb rotates 90° laterally → preaxial border and thumb come to lie on the lateral side. Lower limb rotates 90° medially → preaxial border and great toe come to lie on the medial side. 36 Development of limb bones Upper limb: All the bones of upper limb (scapula, clavicle, humerus, radius, ulna, carpals, metacarpals, and phalanges) develop from somatopleuric layer of lateral plate mesoderm. Ossification All the bones of the upper limb are formed by endochondral ossification; however, clavicle is formed by both membranous (mainly) and endochondral ossification. * Clavicle is the first bone to ossify in the entire body. 37 Development of limb bones Lower limb: Like upper limb all the bones of lower limb (hip bone, femur, tibia, fibula, tarsals, metatarsals, and phalanges) develop from somatopleuric layer of lateral plate mesoderm. Ossification Bones of the lower limb ossify in the same fashion as those of the upper limb. 38 39  Clinical correlation Amelia: complete absence of all four limbs. Phocomelia: rudimentary hands and feet are directly attached to the trunk. Meromelia: all three segments of limbs are short. 40  Clinical correlation Amelia, phocomelia, and meromelia are characteristically seen in children whose mothers have used an antiemetic drug – thalidomide (Contergan) – between the 6th and 8th week of gestation. Pregnant women had taken this drug – a sleeping pill and antinauseant Between 1956 – 1962 About 8,000-10,000 children with more congenital malformations – deformities of long bones, intestinal atresia, cardiac anomalies. Children with these abnormalities are called thalidomide babies. 41 Clinical correlation Why has this tragedy occurred? The idea that the embryo is perfectly protected in the uterus from various factors („placenta is a perfect barrier“) At that time it was not known yet that the animal reseach models are not adequate for demonstration of the human congenital defects (f.e. in the mouse embryos at the 300-fold dose there are not malformations) The scientific community was not interested in teratology sufficiently in that time. 42 Clinical correlation Syndactyly (webbed fingers or toes): results from failure of hand and foot webs to degenerate between the digits. Polydactyly: supernumerary digit in hand or foot, most commonly the thumb that may have an extra phalanx. Syndactyly Polydactyly 43  Clinical correlation Lobster claw hand or foot: third digit is missing and the second and fourth digits are separated by a wide cleft. Medial two digits are fused; lateral two digits may also be fused. Talipes or clubfoot: any deformity of foot involving talus is called talipes or clubfoot. Congenital dislocation of hip: the joint capsule is lax at birth and there is underdevelopment of acetabulum. 44 Clinical correlation Sirenomelia (sympodia): in this condition, the lower limbs are fused. Foot may be separated or fused. 45 Development of the joints Mesenchymal tissue between two bones differentiates to form joint during 6th and 7th weeks of IUL. Type of joint depends on the differentiation of mesenchyme: o If mesenchyme differentiates into fibrous tissue - fibrous joint (syndesmosis). o If mesenchyme differentiates into cartilage - cartilaginous (primary or secondary cartilaginous joint). o If mesenchyme differentiates into three layers and middle layer degenerates to form joint cavity and synovial membrane - synovial joint. 46  Development of muscular system. Introduction All the muscles of the body are derived from mesoderm except muscles of iris, arrector pili of skin and myoepithelial cells of glands. These are derived from ectoderm (neural crest). Muscles are classified as follows: A. Striated muscles: show cytoplasmic striations of actin and myosin filaments. Types: 1. Skeletal muscles: responsible for the movement of bones and are derived from paraxial mesoderm (somites). 2. Cardiac muscle - myocardium and develop from splanchnopleuric mesoderm. B. Smooth muscles: do not show cytoplasmic striations (hence, smooth) and develop from splanchnopleuric mesoderm. 47 Development of skeletal muscles Skeletal muscles develop from somites. Each somite has dorsolateral dermomyotome and venteromedial sclerotome. Dermomyotome differentiates into superficial dermatome and deep myotome. 48 Development of skeletal muscles Mesenchyme of myotome differentiates into myoblasts (primordial muscle cells). Myoblasts elongate and fuse at ends with each other to form multinucleated myotube (syncytium) Myotubes synthesize muscle proteins (actin, myosin, troponin and so on) and become muscle fibres. Muscle proteins push the nuclei to periphery. Adjacent muscle fibres form bundles, fascicle and complete muscle. 49  Development of individual group muscle Skeletal muscles can be grouped on the basis of development into: 1. Muscles of trunk (body wall), 2. Muscles of branchial arches, 3. Extraocular muscles, 4. Muscles of tongue, 5. Muscles of limbs. 50 Development of extraocular muscles, tongue Extraocular muscles develop from 3 preotic myotomes. Supplied by CNIII, CNIV, CNVI. All the muscles of tongue (extrinsic and intrinsic) except palatoglossus are derived from 4 occipital myotomes. 51 Muscles of body wall Develop from myotomes of somites. Each myotome has two parts: A. Epaxial part (epimere): smaller dorsal part. – Forms extensor muscles of vertebral column; e.g., erector spinae. B. Hypaxial part (hypomere): larger ventral part; forms: – Intercostal muscles – Muscles of anterior abdominal wall – Muscles of neck (longus coli, longus capitis and scalene muscles) – Muscles of ventral midline longitudinal column or strap muscles (rectus abdominis, rectus sternalis, infrahyoid muscles). 52 Muscles of pharyngeal arches (were discussed last semester) Muscles of pharyngeal arches develop from mesoderm of pharyngeal arches. Muscular derivatives of pharyngeal arches: 1st arch: muscles of mastication (temporalis, masseter, lateral and medial pterygoid), tensor tympani, tensor veli palatini, anterior belly of digastric, mylohyoid 2nd arch: muscles of facial expression, posterior belly of digastric, stapedius, stylohyoid 3rd arch: stylopharyngeus 4th arch: cricothyroid, constrictors of pharynx, muscles of palate except tensor vili palatini 6th arch: intrinsic muscles of larynx except cricothyroid *5th arch degenerates; 6th arch is rudimentrary in human, not shown in the pic. 53 Development of muscles of the limbs In the 5th week, myotomes of limb bud form anterior and posterior condensations. Anterior mesenchymal condensation forms: flexor and pronator muscles in upper limb, extensor and adductor muscles in lower limb. Posterior mesenchymal condensation forms: extensor and supinator muscles in upper limb, flexor muscles in lower limb. 54 What is the embryonic source of the origin of the muslces of the tongue except palatoglossus? A. Cervical myotomes B. Mesoderm of the branchial arches C. Occipital myotomes D. Preotic myotomes E. Thoracic myotomes 55  Development of smooth muscle Mesenchymal tissue differentiates into myoblast that later forms spindle-shaped smooth muscle cells – myocytes. Sources for smooth muscles: 1. Splanchnopleuric mesoderm - smooth muscles of GIT and respiratory tract. 2. Intermediate mesoderm - smooth muscles in urogenital system. 3. Surrounding mesenchyme - smooth muscles in developing vessels. 4. Neuroectoderm of optic cup - muscles of iris (sphincter and dilator pupilae) and ciliaris muscle. 5. Ectoderm - arrector pili muscles of skin and myoepithelial cells of mammary gland. 6. Serum response factor (SRF) (transcription protein) is responsible for differentiation of smooth muscle cell differentiation. Myocardin and myocardin- related transcription factors are cofactors that enhance the activity of SRF. 56 Development of cardiac muscles Cardiac muscle develops from mesenchyme of myoepicardial mantle (part of splanchnic mesoderm). Histogenesis of cardiac muscle In cardiac muscle development, each myoblast elongates and gives rise to numerous side branches. These side branches of adjacent cells come in contact with each other. At the point of contact, cell membrane modifies to form intercalated disc → cardiac muscle does not form true syncytium 57 REFERENCES