SEM_14_Musculoskeletal system_PARTE1.docx

Musculoskeletal system Learning objectives Describe the origin of the muscles. Describe the origin of the axial skeleton. Describe the origin of the appendicular skeleton. Understand the development of homologous tetrapod limbs. Describe briefly the development of the head. Consider some...

Musculoskeletal system Learning objectives Describe the origin of the muscles. Describe the origin of the axial skeleton. Describe the origin of the appendicular skeleton. Understand the development of homologous tetrapod limbs. Describe briefly the development of the head. Consider some congenital abnormalities in the development of the musculoskeletal system. Development of the musculature There are three types of muscle tissues: striated (skeletal), smooth and cardiac muscle tissues. Myogenesis of skeletal muscles. Skeletal muscles of the trunk derive from myotomes, and thereby from the segmented paraxial mesoderm which forms the somites. Skeletal muscles of the head have a more complex origin. On the one hand, some of the head musculatures derive from the cranial paraxial mesoderm located anterior to the somites. Unlike the paraxial mesoderm in the trunk, the cranial paraxial mesoderm lacks any overt signs of segmentation. On the other hand, most of the craniofacial muscles are contributed by the branchial mesenchyme, which is considered to be an ectodermal derivative (ectomesenchyme) migrated from the neural crests. - Striated muscles are also called skeletal muscles because they are attached to bones via tendon. To form the striated muscles, mesenchymal cells of the myotomes must differentiate into muscular progenitors called myoblasts. Contiguous myoblasts fuse one another to form multi-nucleated muscular cells called myocytes, also known as muscle fibres. During muscular development, myoblasts synthesise myosin and actin, the contractile myofilaments which alignment produces the striated muscle appearance. Differentiated muscles can preserve a residual population of myoblasts, which are referred to as satellite cells (myosatellite cells). These cells remain adjacent to the muscle fibres and under certain circumstances, they are able to differentiate into new muscle fibres. In undamaged muscle, most of the satellite cells are quiescent; they neither differentiate nor undergo cell division. In response to mechanical strain, satellite cells become activated and proliferate as skeletal myoblasts. https://sway.office.com/yWTQKQ6u2mrsRcAT#content=8k5wHpA7PFsst9 - Animation about muscle differentiation As a broad generalisation, deep muscles of the trunk come from individual myotomes; thereby, they remain usually short and arranged in a metameric pattern. On the other hand, large superficial muscles are usually formed by the fusion of several adjacent myotomes which merge forming extensive and unsegmented musculature. To become functional and reach the proper length, developing muscles must be innervated and stretched by tendons inserted in growing bones. For that reason, spinal nerves become connected to the myotomes from an early stage of development in a metameric or segmental pattern. Axons of the developing spinal nerves establish early connections with the adjacent muscle fibres, forming the basis of what is known as motor units: the muscle fibres innervated by a single motor nerve fibre. As myoblasts migrate to assume adult positions, this segmental innervation maintains its connection with their innervation targets. Because some myotomes must migrate far away during development, the course of the associated nerves must follow along, which may result in long and complicated nerve trajectories. That is the case of the recurrent laryngeal nerve, phrenic nerve or sciatic nerve, among others. - A motor unit defines a single motorneuron together with all the muscle fibres it innervates Initial myotomes divide into two components: a dorsal mass (epimere), innervated by dorsal branches of spinal nerves, and a ventral mass (hypomere), innervated by ventral branches of spinal nerves. The epimere is the origin of the epaxial or dorsal muscles while the hypomere gives rise to the hypaxial or ventral muscles. From a functional perspective, they can be considered two antagonist components: extensor (dorsal) and flexor (ventral) musculature. Subsequently, the two groups subdivide into the individual extensor muscles and flexor muscles. https://sway.office.com/yWTQKQ6u2mrsRcAT#content=iOMHPBng4ys1mC - Migration of the initial myotomes gives rise to the epaxial or dorsal musculature and to the hypaxial or ventral muscles. - In the trunk, myogenic cells of skeletal muscles have two distinct embryonic origins. Myogenic cells of the dorsal muscle derive from the epaxial part of the myotomes (blue), while myogenic cells of the ventral muscles, diaphragm and limb muscles derive from the hypaxial part of the myotomes (pink). Myogenesis of cardiac muscle Cardiac muscle is derived from the visceral splanchnic mesoderm surrounding the heart tube. As in the skeletal musculature, cardiac myoblasts produce the same myofilaments (myosin and actin), but instead of fusing to each other to form long muscle fibres, in the heart, each individual myoblast gives rise to one cardiac cell muscle. Myoblasts adhere to one another by special attachments that later develop into what is called intercalated discs. Thereby, cardiac fibres although they are striated, they are shorter than the skeletal muscle fibres, and usually, they contain only one nucleus. - Cardiac muscle intercalated discs are part of the cardiac muscle sarcolemma and they contain gap junctions and desmosomes. Myogenesis of smooth muscle Smooth muscles associated with thoracic and abdominal viscera derive from the surrounding splanchnic or visceral mesoderm. In other structures, such as blood vessels and hairs, the smooth musculature differentiates from the local mesoderm. An exception to this mesodermal origin of the smooth musculature is the ciliary and pupillary muscles of the eye, which derive from ectomesenchyme migrated from the neural crests. In smooth muscle differentiation, myoblasts produce the same contractile proteins as in skeletal and cardiac muscle, but they do not have visible striations because these contractile proteins are laid out in a different pattern. Also, in contrast with the skeletal fibres, smooth muscle cells are shorter and with one nucleus because each of them differentiates from one individual myoblast. - Smooth muscle fibres are spindle-shaped (wide in the middle and tapered at both ends, somewhat like a football) and have a single nucleus. Bone development Embryologically, the skeleton originates from mesenchyme that comes from different sources: Paraxial mesoderm. Mesenchyme from the sclerotomes gives rise to the axial skeleton (vertebral column and rib) by endochondral ossification. Also, the cranial paraxial mesoderm contributes to forming of the bones of the base of the cranium by endochondral ossification. Branchial mesenchyme. The branchial ectomesenchyme derived from the neural crest forms the bones of the roof of the cranium and facial skeleton by intramembranous ossification. Lateral mesoderm. Mesenchyme from the parietal mesoderm invades the growing limbs to give rise to the appendicular skeleton (bones of the limbs) by endochondral ossification. Osteogenesis or ossification is the process of forming new bone tissue by stem cells called osteoblasts. There are two processes by which new bones can be produced: Intramembranous ossification, or direct ossification, gives rise to ossified bones directly from sheets of mesenchymal (undifferentiated) connective tissue. Endochondral ossification, or indirect ossification, involves the formation of a first skeleton made of cartilaginous bones, which are gradually replaced by ossified bones. - Ossification is the process of creating new bone material by cells called osteoblasts. There are two processes to form normal bone tissue: Intramembranous ossification is the direct formation of bone from primitive connective tissue (mesenchyme), while endochondral ossification involves cartilage as a precursor. Intramembranous ossification The flat bones of the face, most of the cranial bones, and the clavicles (collarbones) are formed via intramembranous ossification. It is also an essential process during the natural healing of bone fractures. Unlike endochondral ossification, osteoblasts arise directly from mesenchyme cells without differentiating any previous cartilage stage. This process includes the formation of: Ossification centres. Clusters of mesenchymal cells which differentiate into osteoblasts. Matrix. Osteoblasts start to secrete fibres (proteins) which become organised into a bony matrix called osteoid. Soon after, the osteoid combines with calcium to form the calcified bone. This calcified bone engulfs the osteoblasts inside of spaces called lacunae where they become mature bone cells or osteocytes. Bone differentiation. The osteoid is continually laid down and calcified around blood vessels. Structures like little beams, called trabeculae, are formed around the vessels giving rise to the spongy bone. As the trabeculae thicken within the spongy bone, the osteoblasts on the periphery continue to lay down new layers of osteoid which condense to form the compact bone around the spongy bone. On both sides of the newly formed bone, the surrounding fibrous tissue condenses to form the periosteum. Bone remodelling. The final bone is the result of two opposite processes. While new bone tissue is formed by the osteoblast (a process called ossification), some parts of the newly formed bone are removed by the osteoclasts (a process called bone resorption). Osteoclasts are large polynucleated cells that are formed by the fusion of several mononuclear cells derived from a blood stem cell from the bone marrow displaying many properties of macrophages. The formation and resorption processes control the reshaping of the bones and give rise to the structural features of the bones. The remodelling of the flat bones leads to the formation of two outer plates of compact bone which encloses an inner network of spongy bone (also called diploe). Inside the spongy bone, the vascular tissue gives rise to the bone marrow. In the skull, the intramembranous bones articulate by means of fibrous joints called sutures. Widened suture areas, at the corners of growing bones, are called fontanels (also spelt fontanelles). Sutures and fontanels allow bony plates to overlap one another to facilitate the passage of the head through the birth canal. https://sway.office.com/yWTQKQ6u2mrsRcAT#content=jEPuTB69uPS2Iq - In the intramembranous ossification, the embryonic connective tissue (mesenchyme) turns directly into bone tissue. Although it is simpler and phylogenetically appears earlier than endochondral ossification, the intramembranous ossification only occurs in flat bone formation (skull, maxilla, mandible, pelvis, clavicle, subperiosteal surface of the long bones). This process also plays an essential role during the natural healing of bone fractures. Endochondral ossification Endochondral ossification is a two steps process. Initially, the mesenchyme differentiates into a cartilage model (cartilaginous skeleton). Then, during foetal development and postnatal growth, this model is gradually replaced by bones. Some major steps included in the endochondral ossification are: Local mesenchyme undergoes condensation and differentiates into chondroblasts. Chondroblasts secrete a cartilaginous matrix which differentiates into a model of the future bone made of cartilage tissue: cartilaginous bone precursor; this model is surrounded by perichondral fibrous tissue called perichondium. The cartilaginous model undergoes further ossification by the development of primary and secondary ossification centres. In long bones, the shaft called diaphysis is ossified by a primary ossification centre, whereas the rounded ends called epiphyses undergo ossification by secondary ossification centres. The timing of ossification is related to the maturity stage of the skeleton at birth what differs greatly in different species. In general, the diaphyses are ossified during embryonic development, whereas ossification of the epiphysis does not usually start until after birth. Rests of the cartilage template from which long bones developed remain in two areas: over the surface of the epiphysis as the articular cartilage and between the epiphysis and diaphysis as growth plates. Growth plates, also known as physis or epiphyseal plates, are located between the diaphysis and the epiphyses. The growth plates are responsible for increasing the length of the bone; therefore, ossification is postponed in these areas until the growth plates become ossified and the bones stop growing in length in late adolescence or early adulthood. Articular cartilages line the surfaces of the bones where they contact adjacent bones to form part of the joints. Bones are surrounded by a fibrous layer called the periosteum (former perichondrium) which is responsible for the growth of bones in diameter. https://sway.office.com/yWTQKQ6u2mrsRcAT#content=9m9wE2ECP9skP5 - Endochondral ossification is the process by which growing cartilage is systematically replaced by bone to form the growing skeleton. The sites of ossification occur in the primary centre of ossification, which is in the middle of the diaphysis (shaft) and then in the secondary centre of ossifications, which are in each end (epiphysis) of long bones. The cartilage between the primary and secondary ossification centres is called the epiphyseal plate, and it allows the grow in the length of the bone. The growth in diameter of bones around the diaphysis occurs by the deposition of bone beneath the periosteum. Joint development Adjacent cartilaginous models of bones are connected by a condensation of mesenchyme which produces an interzone region or joint. According to the nature of the future joint, the interzone becomes fibrous connective tissue (fibrous joints), fibrocartilage tissue (cartilaginous joints) or a synovial cavity (synovial joints). Synovial joint formation. Mesenchyme at the centre of the interzone undergoes cavitation to form the synovial cavity. Tissue bordering the cavity becomes the synovial membrane while uneven expansions of the cavity create the synovial folds. The interzone mesenchyme also forms intra- articular ligaments where these are present. Perichondral tissue surrounding the interzone becomes the joint capsule and localised thickenings of the joint capsule give rise to the ligaments. Nerve driven muscle activity is essential for proper synovial joint development after the joint cavity is formed. Joints must move during in utero and postnatal development to prevent ankylosis (fixed/frozen joint). https://sway.office.com/yWTQKQ6u2mrsRcAT#content=T275StyghES3hu - Joints develop in the places where bones come together. Depending on the mobility of the articulation, the mesenchyme which forms an inter-zonal region between the ends of developing bones gives rise to specific anatomical structures and tissues. Accordingly to these features joints may be classified in three types: synovial, fibrous or cartilaginous. Axial skeleton It comprises vertebrae, ribs and sternum. Vertebrae Development of the vertebrae begins with the accumulation of mesenchyme cells from each sclerotome around the notochord. These cells differentiate into a hyaline cartilage model for each vertebra, which then grows and eventually ossifies into bone tissue through the process of endochondral ossification. The formation of the vertebral bodies is preceded by a re-segmentation of the original sclerotomes. In the pre-cartilage stage, sclerotomes surrounding the notochord split and differentiates into cranial (diffuse) and caudal (dense) regions per original sclerotome. To produce a cartilage model of one vertebra, the diffuse region from one somite combines with the dense region of the adjacent somite. That is, the caudal half of each sclerotome joins the cephalic part of the adjacent sclerotome resulting in the origin of one vertebral body. Because of the vertebral re-segmentation, vertebrae are shifted relative to other segmental structures such as spinal muscles or spinal nerves. This rearrangement of the vertebral column allows the intervertebral muscles to span adjacent vertebrae and the spinal nerves traverse intervertebral foramina. Dorsally to the vertebral body, the mesenchyme proliferates to form the vertebral arch which encloses the neural tube within the vertebral canal. Ventrolaterally, the mesenchyme forms the transverse and costal processes. The latter will form the ribs in the thorax. Intervertebral disc regions develop between newly formed adjacent vertebrae. In this intervertebral space, the mesenchyme forms the annulus fibrosus of the intervertebral disc and the rest of the notochord persist as the nucleus pulposus of the vertebral disc; elsewhere notochord degenerates and disappears. https://sway.office.com/yWTQKQ6u2mrsRcAT#content=lfZs4ttt62Y5cY - The development of the vertebrae begins with the accumulation of mesenchyme cells from each sclerotome around the notochord. These cells differentiate into a hyaline cartilage model for each vertebra, which then grows and eventually ossifies into the bone through the process of endochondral ossification. Ribs and Sternum The ribs are formed when, in the thoracic region, the costal processes of the vertebrae extend ventrolaterally to protect the lungs and heart. These mesenchymal extensions become cartilaginous during the embryonic stage and ossify during the foetal period, except their distal ends which remain as costal cartilages. Depending on the species, the costal cartilages of the first pairs of ribs, referred to as sternal ribs, (first 9 pairs in dogs, first 8 pairs in ruminants and horses and 7 pairs in pigs) join to the sternum in the ventral midline. The remaining pairs of developing ribs referred to as asternal ribs, do not reach the sternum but instead fuse to the preceding rib to form the costal arch. The sternum is formed by the union in the median plane of two cartilaginous sternal bars situated one on either side of the ventral body wall. These two longitudinal bars, which are connected with the costal cartilages of the sternal ribs, converge at the ventral midline and fuse along the middle line to form the cartilaginous primordium of the sternum. Following fusion, endochondral ossification gives rise to a number of individual bone components of the sternum called sternebrae. https://sway.office.com/yWTQKQ6u2mrsRcAT#content=iGdmwB6CfAP3Bt - The ribs initially develop as part of the cartilage model for each vertebra, but in the thorax region, the costal processes separate from the vertebra. The cartilage model of the rib then ossifies, except for the anterior portion, which remains as the costal cartilage. The sternum initially forms as paired hyaline cartilage models on either side of the anterior midline. Appendicular skeleton The limbs of domestic animals start to develop as four protrusions on the surface of the body called limb buds, two in the cervicothoracic region (forelimbs or thoracic limbs) and two in the lumbosacral region (hindlimbs or pelvic limbs). Each limb bud is produced by localised proliferation and condensation of parietal mesenchyme covered by the ectoderm. The ectoderm along the outer margin of the limb bud forms a thickened edge called apical ridge. The formation of the apical ridge is induced by the underlying mesoderm but, in turn, it induces the mesoderm to continue growing into a limb. https://sway.office.com/yWTQKQ6u2mrsRcAT#content=PYuValVu1y0xzP - The mesodermal masses of the limb proliferate, and, covered with the thickened epidermis, form on the surface of the body conical protrusions called the limb buds Insofar as the myogenic precursor cells migrate from the somites into the limb bud, branches of the spinal nerves enter into the developing limb. The embryonic development of the limbs consists basically in the elongation of the buds while the filling somatic mesoderm and migrated myoblast from somites located at the level of the limbs give rise to the musculoskeletal components. Regional differentiation of the limbs involves a three-dimensional pattern of development: proximal- distal (shoulder-finger or hip to toe), medial-lateral (digit 1 to digit 5), and dorsal-ventral (knuckle- palm). This pattern of morphogenesis is regulated by three specific signaling centers that create three specific morphogenic gradients for each zone of the developing limb. https://sway.office.com/yWTQKQ6u2mrsRcAT#content=EdLQK3iMJhqYbM - Cellular signalling centres in the development of the limbs. According to this special information, the filling mesenchyme differentiates into the specific bones while the migrated myoblasts are initially segregated into an extensor mass and a flexor mass. Subsequently, the two muscular masses subdivide into the individual extensor muscles and flexor muscles. Along with the myoblast migration, the innervation of the limbs is drawn into the limb buds from the corresponding segment spinal cord. https://sway.office.com/yWTQKQ6u2mrsRcAT#content=EFSa5OpHd029lP - Homologies in the development of the thoracic limbs. Forelimbs of mammalian vertebrate as humans, bats, and horses are homologous; the form of construction and the number of bones in these varying limbs are practically identical and represent adaptive modifications of the forelimb structure of their early common mammalian ancestors. https://sway.office.com/yWTQKQ6u2mrsRcAT#content=LkapNIxIQvserr - Homologies in the development of the pelvic limbs. Frogs, birds, horses and humans all have differently shaped hind limbs, reflecting their different lifestyles. But all those different limbs share the same set of homologous bones. Regarding the distal end of the limb buds, all domestic mammals share the same default construction from a handplate/footplate, which consists of a flattened, paddle-shaped region with five radiating digits. Separate digits are produced by programmed cell death (apoptosis) that cause the interdigital zones to degenerate. Species with less than five digits undergo further degeneration and/or fusion of developing digits. Mammals have three stances based upon how the bones in their limbs touch the ground. These stances are plantigrade, digitigrade, and unguligrade. Ungulates use the tips of their digits, which are covered by hooves, to sustain their body weight. They include odd-toed ungulates (perissodactyls), such as horses and rhinoceroses, and even-toed ungulates (artiodactyls), such as cattle, pigs, giraffes, camels, deer, and hippopotamuses. Horses (odd-toed animals) develop one functional finger, the middle toe on each hoof (III) which is usually larger than its rudimentary neighbours (II and IV). - The horse family is one of three families in the mammalian order Perissodactyla. This order includes rhinoceroses, tapirs, horses and zebras. These animals are commonly considered odd-toed ungulates. This refers to their odd number of toes, such as it is found in the one-toed single hoof of the horse or the three-toed split hooves of the tapir. The middle toe on each hoof (III) is usually larger than its neighbours (II and IV). Ruminants and pigs are cloven-hoofed animals (even-toed animals) whose weight is borne by the two middle fingers (III and IV) of approximately equal size and two outer rudimentary fingers (II and V). - Artiodactyls are even-toed ungulates (hoofed mammals). This order includes cloven-hoofed animals whose weight is borne by the two middle fingers (III and IV) of approximately equal size and two outer rudimentary fingers (II and V). Dogs, like most carnivores, are digitigrades (animals that stand or walk on their digits which are provided with long pointed claws). They retain the original embryonic pattern of five digital fingers. Digits 2,3,4 and 5 are weight-bearing while digit 1 (dewclaw) is not weight-bearing and much smaller in size. Dewclaws, like digit 1 in carnivores or digits 2 and 5 in ruminants and pigs, are vestigial digits that do not make contact with the ground when the animal is standing. The name refers to the dewclaw's alleged tendency to brush dew away from the grass. - Digitigrade is an animal that stands or walks on its digits. Most carnivores are digitigrade that retain the original embryonic pattern of five digital fingers. In dogs, digits 2,3,4 and 5 are weight-bearing while digit 1 is not weight-bearing and much reduced in size. Some common congenital defects in the development of the limbs Achondroplasia (a- (“not”) + chondro- (“cartilage”) + -plasia (“growth”). It is a form of short-limbed inherited dwarfismin caused by premature ossification of the growth cartilages of the extremities. Arthrogryposis (from Greek gryposis = crooked). It can result from malformed joints, denervation, abnormal muscle tension, or impaired mobility in utero. Polydactyly (from Greek dactylos = digit). It consists of the presence of extra digits; syndactyly means fused digits; brachydactyly referred to stumpy digits. Amelia (from Greek melos = limb). It is a birth defect of lacking one or more limbs; meromelia: is the absence of part of a limb; micromelia is the condition in which a limb is abnormally small. Polymelia is a birth defect in which an affected individual has more than the usual number of limbs. Phocomelia: It is the absence of the proximal segment(s) of the limb. In human, the largest occurrence of phocomelia cases was a consequence of pregnant women taking thalidomide in the late 1950s. Angular limb deformities are postural deformities in the frontal plane of the limbs with either lateral (i.e., valgus) or medial (i.e., varus) deviation of the limb.