Embryonic Development of the Skeletal and Muscular System PDF

(001) EMBRYONIC DEVELOPMENT OF THE SKELETAL AND MUSCULAR SYSTEM. DR. PABLO QUEDADO | 12/01/20 B....

(001) EMBRYONIC DEVELOPMENT OF THE SKELETAL AND MUSCULAR SYSTEM. DR. PABLO QUEDADO | 12/01/20 B. Endochondral ossification – process in which OUTLINE mesenchymal cells first differentiate into cartilage models I. MUCOSSKELETAL SYSTEM OVERVIEW before undergoing ossification. A. Paraxial Mesoderm - underlies the formation of the base of the skull, some bones B. Parietal Layer of the Lateral Plate Mesoderm of the face, the bones of the limbs and girdles, the vertebral C. Neural Crest Cells column, the ribs, and the sternum. II. AXIAL SKELETON A. Skull Vertebral Column -occurrence of both processes first requires the condensation of B. Ribs mesenchymal cells - the loosely organized embryonic connective C. Sternum tissue. III. CLINICAL CORRELATES -Development of the limbs involves the inductive influences of the apical A. Skull Malformities ectodermal ridge, the formation of circular constrictions to separate B. Vertebral Malformations parts of the limbs, and opposite rotations of the upper and lower limbs. C. Rib Malformations Development of the skeletal muscle involves the differentiation of D. Sternal Malformations myotome cells into myoblasts. IV. LIMB GROWTH and DEVELOPMENT -The base of the skull, some bones of the face, the vertebral column, A. Appendicular Skeleton the ribs, the sternum, and the bones of the limbs and girdles form by a B. End of the 4th Week two-step process: chondrification and ossification. C. 5th Weeks 1. Apical Ectodermal Ridge (AER) 2. Components of Proximodistal Limb Development D. 6-week Old Embryo E. 7th Week 1. Upper Limb 2. Lower Limb F. Ossification of Bones 1. Endochondral Ossification 2. Synovial Joints 3. Fibrous Joints Figure 1. Endochondrial Ossification- histologic side. V. CLINICAL CORRELATION A. Bone Age B. Limb Defects/ Limb malformations JOINTS VI. SKIN During the sixth gestational week, joints begin to develop with the A. Epidermis formation of condensed mesenchyme in the interzone, the region B. Dermis between two bone primordia. VII. HAIR I. CLASSIFIED AS: VIII. HAIR FINGERNAILS and TOENAILS 1. Fibrous Joints- involves mesenchymal cells in the interzone IX. SWEAT GLANDS i.e. sutures of the skull A. Eccrine 2. Cartilaginous Joints- involves mesenchymal cells in the interzone B. Apocrine to differentiate into hyaline cartilage or fibrocartilage X. MAMMARY GLANDS i.e. costochondral joints, pubic symphysis XI. CLINICAL CORRELATES 3. Synovial Joint A. Pigmentary Disorders B. Abnormalities of Hair Distribution II. AXIAL SKELETON C. Mammary Gland Abnormalities involves a more extensive process: the central mesenchymal cells in the interzone undergo apoptosis to form the synovial joint cavities, whereas the peripheral cells differentiate into ligaments and dense I. MUCOSKELETAL SYSTEM fibrous tissue. Develops from three sources: The axial skeleton includes: A. Paraxial mesoderm A. Skull B. Parietal layer of the lateral plate mesoderm B. Vertebral column C. Neural crest cells C. Ribs The development of bone and muscle begins at the fourth gestational D. Sternum. week, when the paraxial mesoderm differentiates into somites; the Skeletal system develops from paraxial and lateral plate latter gives rise to sclerotomes and dermomyotomes. Sclerotomes (parietal layer) mesoderm and from neural crest. form the vertebra and the ribs, whereas myotomes form the majority of Paraxial mesoderm forms a segmented series of tissue the muscular system. blocks on each side of the neural tube, known as somitomeres in the head region and somites from the occipital region caudally. BONES Somites differentiate into a ventromedial part, the Bone formation (osteogenesis) can occur either: sclerotome, and a dorsolateral part, the dermomyotome. A. Intramembranous ossification – process in which At the end of the fourth week, sclerotome cells become mesenchymal cells ensheathed in membranous tissue directly polymorphous and form loosely organized tissue, called undergo ossification. mesenchyme, or embryonic connective tissue. - underlies the formation of the cranial vault, many bones of It is characteristic for mesenchymal cells to migrate and to the face, and the clavicle. differentiate in many ways. They may become fibroblasts, chondroblasts, or osteoblasts (bone-forming cells). PREPARED BY: CMED 1D Page 1 of 12  (001) EMBRYONIC DEVELOPMENT OF THE SKELETAL AND MUSCULAR SYSTEM. DR. PABLO QUEDADO | 12/01/20 Figure 2. Development of Solomite - [A] Paraxial mesoderm cells are arranged around a small cavity. [B] As a result of further differentiation, cells in the ventromedial wall lose their epithelial arrangement and Figure 3. Skull of a newborn. [A] seen from above, [B] and right side become mesenchymal collectively called sclerotome. SKULL The skull can be divided into two parts: A. Neurocranium B. Viscerocranium A. Neurocranium - forms a protective case around the brain NEUROCRANIUM has 2 portions: 1. Membranous Neurocranium, consisting of flat bones, which surround the brain as a vault The membranous portion of the skull is derived from neural crest cells and paraxial mesoderm. Mesenchyme from these two sources invests the brain and undergoes intramembranous ossification. Figure 4. Parts of the skull. The result is formation of a number of flat, membranous bones that are characterized by the presence of needle-like bone spicules. 1.1 Newborn Skull 2. Cartilaginous Neurocranium, or chondrocranium, which forms At birth, the membranous bones are separated bones of the base of the skull. from each other by dense connective tissue o The neural crest cells form the prechordal chondrocranium membranes that form fibrous joints, known anterior to the center of the sella turcica, whereas the As the cranial sutures (coronal, sagittal, and paraxial mesoderm form the chordal chondrocranium lambdoid) posterior to the center of the sella turcica. At points where more than two bones meet, sutures are wide o The development of the base of the skull is complete when and are called fontanelles these cartilaginous structures fuse and undergo endochondral ossification. o Anterior fontanelle, is the most prominent, which o Structures derived from the chondrocranium include is found where the two parietal and two frontal components of the occipital bone, the sphenoid bone, and bones meet. the ethmoid bone, specifically the: o Posterior fontanelle is found where the parietal Posterior half of the cribriform plate bones and the occipital bone meet. Lesser wings of the sphenoid o Posterolateral (mastoid) fontanelles are found Greater wings of the sphenoid where the parietal, occipital, and temporal bones Sella turcica meet. Petrous part of the temporal bones and the adjacent Soon after birth, membranous bones move back to parts of the occipital bone their original positions, and the skull appears large Clivus and round. Condyles of the occipital bone Several sutures and fontanelles remain membranous for a considerable time after birth. A 5- to 7-year-old child has nearly all of his or her cranial capacity, some sutures remain open until adulthood The anterior fontanelle closes by 18 months of age, and the posterior fontanelle closes by 1 to 2 months of age. The mastoid fontanelle by 6 months, and the cranial suture by 36 months. PREPARED BY: CMED 1D Page 2 of 12  (001) EMBRYONIC DEVELOPMENT OF THE SKELETAL AND MUSCULAR SYSTEM. DR. PABLO QUEDADO | 12/01/20 By the fourth gestational week , sclerotome cells surround the neural tube and the notochord to merge with cells derived from the opposing somite. Each sclerotome then undergoes resegmentation, a process that involves the caudal half of each sclerotome to fuse with the cranial half of each adjacent sclerotome; this forms the centrum, the primordial vertebral body. Thus, each vertebra develops from two adjacent sclerotomes rather than from one sclerotome. Not all cells in the caudal half of each sclerotome undergo re- segmentation. Instead, some migrate cranially and contribute to the formation of the intervertebral disc. Figure 5. Dorsal view of Chondrocranium - Showing bones formed by RIBS enochondrial ossification in adult. As development continues, the notochord completely degenerates in the centrum, but where it persists, it enlarges Viscerocranium - forms the skeleton of the face. as a gelatinous center. This forms the nucleus pulposus, Formed by the first two pharyngeal arches. which is later surrounded by circularly arranged fibers known The first pharyngeal arch undergoes intramembranous ossification to as the annulus fibrosis. Combined, these two structures form give rise to the: the intervertebral discs. o Zygoma By the sixth gestational week, the sclerotome cells o Maxilla surrounding the neural tube form a cartilaginous vertebral o Squamous part of the temporal bone arch, and fuse with the cartilaginous vertebral body. o Mandible The spinous, transverse, and costal processes develop as The dorsal tip of the mandibular process and the second pharyngeal extensions from this newly assembled cartilage model. arch undergo endochondral ossification to give rise to the malleus, the In the lumbar region, the costal processes of the first sacral incus, and the stapes. vertebrae fuse and form the lateral sacral mass, known as the ala of the sacrum. The ventral portion the mandibular process, contains the Meckel The process of chondrification continues until a cartilaginous cartilage. Mesenchyme around the Meckel cartilage condenses and vertebral column is fully formed. ossifies by intramembranous ossification to give rise to the mandible. Two primary curves of the spine is established: The Meckel cartilage disappears except in the sphenomandibular Thoracic and Sacral curvatures; Later, two secondary ligament. The dorsal tip of the mandibular process, along with that of curves are established: Cervical curvature, as the child the second pharyngeal arch, later gives rise to the incus, the malleus, learns to hold his head up, and the Lumbar curvature, which and the stapes forms when the child learns to walk. The ossicles are the first bones to become fully ossified, with their ossification beginning in the fourth month of gestation. At first the face is small in comparison with the neurocranium. This appearance is caused by: (1) virtual absence of the paranasal air sinuses (2) the small size of the bones, particularly the jaws. With the appearance of teeth and development of the air sinuses, the face loses its babyish characteristics. Figure 7. Developing regions of somite - [A] cross section, [B] Typical vertebra with its components. Figure 6. Older Fetus - Head and neck region (Lateral View) Figure 8. Formation of Vertebral Column - [A] 4th week, [B] Proliferation of the caudal half of one sclerotome proceeds into the intersegmental mesenchyme and cranial half of the sub adjacent VERTEBRAL COLUMN sclerotome, [C] Vertebrae are formed by the upper and lower halves of Develops from the sclerotomes, the ventromedial part of the the successive sclerotome and the intersegmental tissue. somite. A typical vertebra consist of a vertebral arch and foramen (through which the spinal cord passes), a body, transverse process, and a spinous process. PREPARED BY: CMED 1D Page 3 of 12  (001) EMBRYONIC DEVELOPMENT OF THE SKELETAL AND MUSCULAR SYSTEM. DR. PABLO QUEDADO | 12/01/20 Ribs develop from the costal processes of the thoracic EFNB1 encodes ephrin-B1, a ligand for EphB vertebrae. receptors that causes cells to repel each other, a They are cartilaginous during the embryonic period and kind of antiadhesive activity and important for undergo ossification during the fetal period. preventing premature suture closure The original site where the costal process is connected to the Loss of function mutations in EFNB1 causes vertebra becomes replaced by costovertebral synovial joints. craniofrontonasal syndrome The first seven pairs of ribs attach to the sternum through their Mutations in MSX2 cause Boston-type own cartilages. The subsequent five pairs of ribs attach to the craniosynostosis that can affect a number of sternum through the cartilage of the seventh rib. sutures The last two pairs of ribs do not attach to the sternum. Whereas mutations in TWIST1 cause Saethre- Respectively, this forms the true ribs, the false ribs, and the Chotzen syndrome, characterized by coronal floating ribs. suture synostosis and polydactyly. Fibroblast growth factors [FGFs] and fibroblast STERNUM growth factor receptors [FGFRs] play important roles in most of skeletal development. The sternum develops from a pair of separate vertical, condensed bands of mesenchymal cells, known as the FGFR1 and FGFR2 are co-expressed in pre-bone sternal bars. These sternal bars form independently lateral and pre-cartilage regions, including craniofacial to the midline of the ventral body wall. Chondrification occurs structures while the sternal bars migrate medially. FGFR3 is expressed in the cartilage growth plates By the tenth gestational week, they fuse in cranial-to-caudal of long bones and in the occipital region. sequence at the midline and form the cartilage model of the A. Scaphocephaly - Early closure of the sagittal manubrium, the sternal body, and the xiphoid process. suture [57% of cases] results in frontal and occipital expansion, and the skull becomes long and narrow B. Brachycephaly - Premature closure of the III. CLINICAL CORRELATES coronal sutures [20% to 25% of cases] results in a short skull CRANIOFACIAL DEFECTS AND SKELETAL C. Plagiocephaly - If the coronal sutures close prematurely on one side only, then the result is an DYSPLASIAS asymmetric flattening of the skull 1. Neural Crest Cells most common causes of craniosynostosis are Originating in the neuroectoderm genetic Form the facial skeleton and part of the skull Other cases include: Often a target for teratogens o vitamin D deficiency 2. Cranioschisis o exposure to teratogens, including, The cranial vault fails to form and brain tissue diphenylhydantoin, retinoids, valproic acid, exposed to amniotic fluid degenerates, resulting in methotrexate, and cyclophosphamide anencephaly. o intrauterine factors that constrain the fetus, Caused by failure of the cranial neuropore to close such as oligohydramnios and multiple birth Children with such severe skull and brain defects pregnancies. cannot survive. Children with relatively small defects in the skull through which meninges and/or brain tissue herniate [cranial meningocele and meningoencephalocele, respectively] may be treated successfully. Figure 10. Craniosynostosis involving sagittal suture [A], child with Scaphocephaly [B], CT-scans premature closure of sagittal suture [C]. Figure 9. Child with anencephaly [A], Patient with meningocete [B]. 3. Craniosynostosis Caused by premature closure of one or more sutures. These abnormalities are collectively known as craniosynostosis. Crest cells form the frontal bones; paraxial mesoderm forms the parietal bones and the loose mesenchyme in the coronal sutures PREPARED BY: CMED 1D Page 4 of 12  (001) EMBRYONIC DEVELOPMENT OF THE SKELETAL AND MUSCULAR SYSTEM. DR. PABLO QUEDADO | 12/01/20 Figure 11. Craniosynostosis - [A] child with brabrachycephaly, [B] child with plagiocephaly, [C] CT-scan of skull showing Plagiocephaly. 4. Skeletal Dysplasias A. Achondroplasia [ACH] - most common form of skeletal dysplasia [1/20,000 live births], primarily affects the long bones. Figure 13. Cleidocranial dysotosis. RIB DEFECTS 1. Klippel-Feil Syndrome Involves the fusion of cervical vertebrae, which results in reduced mobility, short neck, and low hairline. 2. Spina Bifida Failure of vertebral arches to fuse, thus generally exposing the spinal cord in the sacral region. In spina bifida occulta, there are minimal neurological deficits; the spinal cord is intact and is covered by skin. In spina bifida cystica, the meninges and/or the Figure 12. Achondroplasia - Child with cleidocranial dysostosis with neural tissue protrude through the skin at the sacral generalized skeletal dysplasias. region to form a cyst-like sac. More severe B. Thanatophoric dysplasia – most common abnormality. neonatal lethal form of skeletal dysplasia [1/40,000 live births] 2 TYPES (both are autosomal dominant) VERTEBRAL DEFECTS Type I is characterized by short, curved femurs with or 1. Accessory ribs are usually rudimentary and unilateral or without cloverleaf skull bilateral; they develop from the costal processes of cervical or lumbar vertebrae. Type II individuals have straight, relatively long femurs and 2. Cervical ribs are usually attached to the seventh cervical severe cloverleaf skull caused by craniosynostosis vertebrae. Another term for cloverleaf skull is Kleeblattschadel, occurs when all 3. Lumbar ribs are usually clinically insignificant, whereas of the sutures close prematurely, resulting In the brain growing cervical ribs may impinge on the brachial plexus or subclavian through the anterior and sphenoid fontanelles. vessels, resulting in varying degrees of anesthesia of the C. Hypochondroplasia - another autosomal dominant upper limbs. form of skeletal dysplasia, appears to be a Fused ribs occur posteriorly when two or more ribs arise from mildertype of ACH. Common to all of these forms of a single vertebra. skeletal dysplasias are mutations in FGFR3 causing abnormal endochondral bone formation so that growth of the long bones and the base of the skull DEFECTS IN STERNUM are adversely affected. 1. Cleft sternum is the result of a complete or partial midline fusion of the sternal bars. The heart and its major vessels are 5. Generalized Skeletal Dysplasia covered only by skin and soft tissue and thus are unprotected. A. Cleidocranial dysostosis - an example of a 2. Pectus excavatum (hollow chest) involves a concave generalized dysplasia of osseus and dental tissues depression of the sternum. that is characterized by late closure of the 3. Pectus carinatum (keel-shaped chest) involves an anterior fontanelles and decreased mineralization of the projecting sternum. Both congenital deformities are often cranial sutures resulting in bossing [enlargement] of asymptomatic but may impair cardiac and respiratory function the frontal, parietal, and occipital bones. Other parts depending on the severity. of the skeleton are affected as well, and oftentimes, the clavicles are underdeveloped or missing. PREPARED BY: CMED 1D Page 5 of 12  (001) EMBRYONIC DEVELOPMENT OF THE SKELETAL AND MUSCULAR SYSTEM. DR. PABLO QUEDADO | 12/01/20 2. The posterior fontanelle usually closes by age _____. a. 1 to 2 months b. 1 to 2 years c. 3 to 6 months d. 3 to 6 years 3. Mesenchyme around the Meckel cartilage condenses and ossifies by intramembranous ossification to give rise to the______. a. Maxilla b. Mandible c. Morulla d. Mesenchyme 4. It is the most common form of skeletal dysplasia and primarily affects the long bones. a. Thanatophoric dysplasia b. Aachondroplasia c. Hypochondroplasia 5. Another term for cloverleaf skull which occurs when all of the sutures close prematurely, resulting in the brain growing through the anterior and sphenoid fontanelles a. Craniosynostosis b. Type II Thanatophoric dysplasia c. Kleeblattschadel 6. What do you call the premature closure of the coronal sutures that result in a short skull a. Brachycephaly b. Scaphocephaly Table 1. Genes associated with skeletal defects. c. Plagiocephaly 7. ________ is the result of a complete partial midline fusion of the sternal bars. a. Macromegaly b. Cleft sternum c. Pectus carinatum 8. Failure of vertebral arches to fuse, thus generally exposing spinal cord in the sacral region. a. Cleft Sternum b. Klippel-Feil Syndrome c. Spina Bifida 9. An example of generalized dysplasia of osseus and dental tissues that is characterized by late closure of the fontanelles and decreased mineralization of cranial sutures resulting in bossing (enlargement) of the frontal, parietal, and occipital bones. a. Cleidocranial dysostosis b. Spina Bifida c. Kleppel-Feil Syndrome 10. An Abnormality in which the brain fails to grow and as a result, skull fails to expand. a. Acromegaly b. Micromegaly c. Sleft Sternum Table 2. Genes associated with skeletal defects. (cont.) IV. LIMB GROWTH AND DEVELOPMENT TEST YOUR KNOWLEDGE (APPENDICULAR SYSTEM) 1. At the end of the fourth week, sclerotome cells become Comprise the limbs including the shoulder and pelvic girdle polymorphous and form loosely organized tissue, called_______. Development of the upper and lower limbs are similar except that morphogenesis of the lower limb is approximately 1-2 a. Somitomeres days behind that of upper limb, whereas the upper and lower b. Mesenchym limbs rotate in opposite directions. c. Neural Crest d. Chondroblast PREPARED BY: CMED 1D Page 6 of 12  (001) EMBRYONIC DEVELOPMENT OF THE SKELETAL AND MUSCULAR SYSTEM. DR. PABLO QUEDADO | 12/01/20 A. END OF 4TH WEEK Hyaline cartilage models are formed by chondrocytes foreshadowing the prospective bones. While the process of The appendicular skeleton includes the bones of the limbs and forming these cartilage models is initiated, synovial joints form girdles between the two chondrifying bone primordia at the interzone. o consist of a core of mesenchymal cells - derived At the center of the cartilage model (diaphysis), primary from the somatic layer of the lateral plate mesoderm ossification centers form where chondrocytes increase in size, - Covered by a layer of ectoderm calcify the matrix, and eventually die. distal border of the limb, the ectoderm forms the apical Blood vessels invade the diaphysis. This results in the ectodermal ridge, (AER) recruitment of osteoblasts, the differentiation of certain The AER exerts an inductive influence on the core of invading cells into hematopoietic cells (blood cells of the bone mesenchymal cells to remain undifferentiated and to rapidly marrow) proliferate; this region is known as the progress zone. The restriction of proliferating chondrocytes towards the distal As the limbs continue to grow, cells farther from the influence ends of the cartilage model (epiphyses of the AER begin to differentiate into cartilage and muscle. Endochondral ossification thus begins from these primary Development of the limbs thus proceed proximodistally. ossification centers at the diaphysis and proceeds toward the Limb buds becomes visible as outpocketings that form ridges epiphyses. However, this process only starts by the end of the on the lateral body wall embryonic period. Forelimb appears first followed by hindlimb 1-2 days D. 7TH WEEK B. 5TH WEEK NOTE: the structural development of the upper limbs and Limbs have attained the bud stage lower limbs are similar but with two exceptions: the Initially, limb buds consist of mesenchymal core derived from development of the lower limb is approximately 1 to 2 days the parietal (somatic) layer of lateral plate mesoderm that will behind that of the upper limb, whereas the upper and lower form the bones and connective tissues covered by cuboidal limbs rotate in opposite directions ectoderm Limbs rotate in opposite directions a. APICAL ECTODERMAL RIDGE (AER) Cells in the mesenchyme differentiate into chondrocytes o Formed from thickened limb from the ectoderm at Joints are formed in the cartilaginous condensations when the distal border chondrogenesis is arrested and joint interzone is induced o Exerts an inductive influence on adjacent Joint cavity is formed by cell death mesenchyme causing it to remain as a population of WNT14 appears to be the inductive signal in joint positioning undifferentiated, rapidly proliferating cells, the a. UPPER LIMB undifferentiated zone b. COMPONENTS OF PROXIMODISTAL LIMB o Rotates 90 degrees laterally placing the extensor DEVELOPMENT muscles lie on the lateral and posterior surface o STYLOPOD and the thumbs lie laterally − Humerus and femur b. LOWER LIMB o ZEUGOPOD o Rotates approximately 90 degrees medially, − Radius/ulna, tibia/fibula placing the extensor muscles on the anterior o AUTOPOD surface and the big toe medially − Carpals,metacarpals,digits/tarsals, digits/metatarsals E. OSSIFICATION of BONES A. ENDOCHONDRAL OSSIFICATION C. 6-WEEK OLD EMBRYO Begins by the end of the embryonic period circular constriction separates the terminal and proximal Primary ossification centers are present in all long bones portions of the limb buds. of the limb by the end of 12th week Second circular constriction divides the proximal portion into 2 Gradually progresses from shaft or diaphysis towards the segments. the familiar parts of the limbs thus become ends of the cartilaginous model recognizable. At birth, diaphysis is usually ossified, but the epiphyses Terminal portion of the limb buds becomes flattened to form are still cartilaginous the hand and footplates and is separated from the proximal Proceeds on both sides of the plate segment by a circular constriction Only after birth, secondary ossification centers develop in Fingers and toes are formed when cell death in the AER the epiphyses, which will also undergo the same separates the ridge into five parts forming webbed fingers ossification and vascularization processes that took place and toe in the diaphysis Further formation of the digits depends on their continued layer of epiphyseal cartilage plate, known as the growth outgrowth under the influence of AER plate, persists between the epiphyses and the diaphysis 1. Five segments of ridge ectoderm Continued proliferation of the chondrocytes in the growth 2. Condensation of mesenchyme to form cartilaginous plate is what allows the diaphysis to lengthen and thus digital rays what maintains the growth of bones 3. Death of the intervening tissues between the rays Only at approximately 20 years of age are when the Further cell death in the interdigital spaces are what creates epiphyses and diaphysis fuse, indicating that skeletal the separation of the digits. By the end of the eight week, digit growth is complete. separation is complete while the fingers develop distal 1. EPIPHYSEAL PLATE swellings known as tactile pads, which are what create Cartilage plate remains between the diaphyseal patterns for fingerprints. and epiphyseal ossification centers Plays an important role in growth in the length PREPARED BY: CMED 1D Page 7 of 12  (001) EMBRYONIC DEVELOPMENT OF THE SKELETAL AND MUSCULAR SYSTEM. DR. PABLO QUEDADO | 12/01/20 Disappears when the bone has acquired full length i. SYNPOLYDACTYLY and epiphyses has unite with the shaft of the bone ▪ Mutations in HOXD13 In long bones, found in each extremity ▪ Combination of syndactyly and polydactyly In smaller bones (phalanges), only found at one j. CLEFT HAND AND FOOT extremity ▪ Consist of an abnormal cleft between the Irregular bones (vertebrae) one or more primary 2nd and 4th metacarpal bones and soft ossification centers and usually several secondary tissues centers present ▪ 3rd metacarpal and phalangeal bones are B. SYNOVIAL JOINTS almost always absent resulting in the Begin to form the same time that mesenchymal possible fusion of the adjacent digits. condensations initiate the process of forming cartilage ▪ Thumb, index finger and 4th and 5th fingers 1. FIBROUS TISSUE maybe fused o Differentiates into articular cartilage, synovial k. HAND-FOOT-GENITAL SYNDROME membranes, mensci ad ligaments within the joint ▪ Mutation sin HOX13 genes capsule ▪ Fusion of the carpal bones and small short C. FIBROUS JOINTS digits The sutures in the skull ▪ Affected females often have partially Formed from interzone regions (bicornuate) or completely (didelphic) divided uterus and abnormal positioning of V. CLINICAL CORRELATION the urethral orifice) 1. BONE AGE ▪ Affected males may have hypospadias Radiologist use the appearance of various l. HOLT-ORAM SYNDROME ossification centers to determine whether a child has ▪ Mutations in TBX5 reached proper maturation age ▪ Characterized by upper limb abnormalities Useful information is obtained from ossification and heart defects (ASD/VSD, conduction studies in the hands and wrist of children abnormalities 2. LIMB DEFECTS ▪ Virtually all defects of upper limb have Malformations of the limbs vary greatly and can include been observed defects in the entirety of the limb, the hand or the foot, and the m. OSTEOGENESIS IMPERFECTA digits. Malformation of the entire limbs include amelia, ▪ Characterized by shortening, bowing and meromelia, phocomelia, and micromelia. hypomineralization of the long bones on the limbs that can result in fractures and Occur approximately in 6 per 10000 live births; blue sclera 3.4/10000 affecting the upper limb; 1.1/10000 the ▪ Mutations in COL1A1 or COL1A2 involved lower limb in type I collagen Often associated with defects involving craniofacial, n. MARFAN SYNDROME cardiac and genitourinary system ▪ Mutations in fibrillin (FBN1) located in Mainly hereditary chromosome 15q21.1 Attributed to the use of Thalidomide between 1957 ▪ Affected individual are usually tall and and 1962 with studies indicating that the most slender with long thin limbs and long thin sensitive period for the induction of limb defects is face between 4th and 5th week of gestation ▪ Other characteristics are sternal defects a. MACROMELIA (pectus excavatum/carinatum),joint ▪ Partial absence of 1 or more extremities hyperflexibility, dilation or dissection of the b. AMELIA ascending aorta and dislocation of the lens ▪ Complete absence of one or more limb of the eye c. PHOCOMELIA o. ARTHROGRYPOSIS (CONGENITAL JOINT ▪ “Seal limb” involves the absence of long CONTRACTURES) bones, resulting in rudimentary hands and ▪ Usually involve more than one joint feet attached to the trunk and pelvis by ▪ Neurological defects (motor horn cell small, irregularly shaped bones deficiency, meningoimyelocele) in origin ▪ Form of meromelia p. CONGENITAL ABSENCE OR DEFICIENCY d. MICROMELIA OR RADIUS ▪ All segments of the extremities are present ▪ Genetic abnormality observed with but abnormally short. malformations in other structures such as ▪ Involves abnormally small limbs. Baller-Gerold Syndrome e. BRACHYDACTYLY (craniosynostosis-radial aplasia ▪ Digits are shortened syndrome) f. SYNDACTYLY ▪ Synostosis in one or more cranial sutures, ▪ 2 or more fingers or toes are fused absence of radius and other defects g. POLYDACTYLY q. AMNIOTIC BANDS ▪ Presence of extra fingers or toes involves ▪ Cause ring constrictions and amputations or digits of limbs or digits ▪ Usually bilateral ▪ From adhesions between the amnion and h. ECTRODACTYLY affected structures of the fetus ▪ Unilateral absence of a digit such as thumb ▪ Originate from the tears in the amnion that detach and surround part of the fetus PREPARED BY: CMED 1D Page 8 of 12  (001) EMBRYONIC DEVELOPMENT OF THE SKELETAL AND MUSCULAR SYSTEM. DR. PABLO QUEDADO | 12/01/20 r. TRANSVERSE LIMB DEFICIENCIES With further proliferation of cells in the basal layer, ▪ Proximal structures are intact, but distal intermediate zone is formed. structures from a transverse plane are at the end of the fourth month, the epidermis acquires its partially or completely absent definitive arrangement and four layers can be distinguished: s. CONGENITAL HIP DISLOCATION 1. Basal layer or germinative layer ▪ Underdevelopment of the acetabulum and - Responsible for production of new cells head of the femur - Later forms ridges and hollows, which are reflected on the surface of the skin in the fingerprint TEST YOUR KKNOWLEDGE 2. Spinous layer - Consist of large polyhedral cells containing fine IDENTIFICATION tonofibrils 1. Characterized by shortening, bowing and hypomineralization 3. Granular layer of the long bones on the limbs that can result in fractures and - Contains small keratohyalin granules in its cells blue sclera 4. Horny layer 2. Often associated with defects involving craniofacial, cardiac - Forms the tough scale-like surface of the epidermis and genitourinary system - Made up of closely packed dead cells containing 3. Combination of syndactyly and polydactyly keratin 4. involves the complete absence of one or more limb Cells of the periderm are usually cast off during the second 5. Affected females often have partially (bicornuate) or part of intrauterine life and can be found in the amniotic fluid. completely (didelphic) divided uterus and abnormal positioning of the urethral orifice) During the first 3 months of development, the epidermis is invaded by cells arising from the neural crest. These cells synthesize melanin pigment in the melanosomes. TRUE or FALSE As melanosomes accumulate, they are transported down 1. After birth, secondary ossification centers develop in the dendritic process of melanocytes. epiphyses, which will also undergo the same ossification and They are now transferred intercellularly to keratinocytes of the vascularization processes that took place in the diaphysis skin and hair bulb. In this manner, pigmentation of the skin and 2. Fibrous tissue differentiates into articular cartilage, synovial hair is acquired. membranes, mensci ad ligaments within the joint capsule 3. Layer of epiphyseal cartilage plate, known as the growth plate, A. DERMIS persists between the epiphyses and the diaphysis Derived from mesenchyme that has three sources: 4. Limb defects ccur approximately in 6 per 10000 live births; Lateral plate mesoderm supplying cells for dermis in the 4.3/10000 affecting the upper limb; 1.1/10000 the lower limb limbs and body wall 5. Synovial joints begin to form the same time that Paraxial mesoderm supplying cells for dermis in the mesenchymal condensations initiate the process of forming back cartilage Neural crest cells supplying cells for dermis in the face and neck Determine whether a given statement/s fall/s under 4 th, 5th, 6th, or During the third and fourth month, the corium, forms 7th of limb development many irregular papillary projections called dermal 1. Upper limb Rotates 90 degrees laterally placing the extensor papillae, which project upward into the epidermis. muscles lie on the lateral and posterior surface and the Dermal papillae thumbs lie laterally -contain a small capillary or sensory nerve end 2. APICAL ECTODERMAL RIDGE Exerts an inductive organ influence on adjacent mesenchyme causing it to remain as a Subcorium population of undifferentiated, rapidly proliferating cells, the -deeper layer of the dermis undifferentiated zone -contains large amount of fatty tissues 3. Distal border of the limb, the ectoderm forms the apical Vernix caseosa ectodermal ridge, (AER) - a whitish paste covering the skin during birth 4. Lower limb rotates approximately 90 degrees medially, - formed by secretions from sebaceous glands and placing the extensor muscles on the anterior surface and the degenerated epidermal cells and hairs big toe medially. -protects the skin against the macerating action of 5. Second circular constriction divides the proximal portion into amniotic fluid. 2 segments. the familiar parts of the limbs thus become recognizable. VI. SKIN the largest organ in the body Origin: - Epidermis- superficial layer, develops from the surface ectoderm - Dermis- deep layer, develops from the mesenchyme. A. EPIDERMIS Initially, the embryo is covered by a single layer of ectodermal cells In the beginning of the second month, this epithelium divides, and a layer of flattened cells, the periderm, or Figure 14. The formation of the skin at various stages of development epitrichium, is laid down on the surface. [A] 5 weeks, [B] 7 weeks, [C] 4 months, [D] Birth. PREPARED BY: CMED 1D Page 9 of 12  (001) EMBRYONIC DEVELOPMENT OF THE SKELETAL AND MUSCULAR SYSTEM. DR. PABLO QUEDADO | 12/01/20 A. ECCRINE VII. HAIR Form in the skin over most parts of the body beginning as buds Begin development as solid epidermal proliferations from the from the germinative layer of the epidermis. germinative layer that penetrates the underlying dermis. At - These buds grow into the dermis, and their end coils to their terminal ends, hair buds invaginate. form the secretory parts of the glands. The invaginations, the hair papillae, are rapidly filled with - Smooth muscle cells associated with the glands also mesoderm in which vessels and nerve endings develop. develop from the epidermal buds. Soon, cells in the center of the hair buds become spindle- These glands function by merocrine mechanisms (exocytosis) shaped and keratinized, forming the hair shaft, whereas and are involved in temperature control. peripheral cells become cuboidal, giving rise to the epithelial hair sheath. B. APOCRINE The dermal root sheath is formed by the surrounding Develop anywhere there is body hair, including the face, mesenchyme. axillae, and pubic region. arrector pili muscle- a smooth muscle attached to the dermal Begin to develop during puberty and arise from the same root sheath epidermal buds that produce hair follicles. Continuous proliferation of epithelial cells at the base of the - Open onto hair follicles instead of skin. shaft pushes the hair upward. The sweat produced by these glands contains lipids, proteins, By the end of the third month, the first hairs appear on the and pheromones, and odor originating from this sweat is due surface in the region of the eyebrow and upper lip. to bacteria that break down these products. Lanugo hair is the first hair that appears and sheds at about A portion of the secretory cells is shed and incorporated into the time of birth and is later replaced by coarser hairs arising the secretion. from new hair follicles. The epithelial wall of the hair follicle usually shows a small bud penetrating the surrounding mesoderm. Cells from these buds X. MAMMARY GLANDS form the sebaceous glands. Cells from the central region of the gland degenerate, forming Mammary lines or mammary ridges a fat-like substance (sebum) secreted into the hair follicle, and - Modified sweat glands and first appear as bilateral from there, they reach the skin. bands of thickened epidermis In a 7-week embryo, these lines extend on each side of the body from the base of the forelimb to the region of the hind limb Although the major part of each mammary line disappears shortly after it forms, a small portion in the thoracic region persists and penetrates the underlying mesenchyme Here it forms 16 to 24 sprouts, which in turn give rise to small, solid buds. By the end of prenatal life, the epithelial sprouts are canalized and form the lactiferous ducts. - lactiferous ducts open into a small epithelial pit Shortly after birth, this pit is transformed into the nipple by proliferation of the underlying mesenchyme. At birth: lactiferous ducts have no alveoli and therefore no Figure 15. The development of a hair and a sebaeceous gland - [A] 4 secretory apparatus. months, [B] 6 months, newborn. At puberty: increased concentrations of estrogen and progesterone stimulate branching from the ducts to form alveoli and secretory cells. VIII. FINGERNAILS and TOENAILS By the end of the third month, thickenings in the epidermis appear at the tips of the digits to form the nail fields - These fields migrate to the dorsal side of each digit and grow proximally, forming the nail root, whereas proliferation of tissue surrounding each nail field creates a shallow depression for each nail. - From the nail root, epidermis differentiates into fingernails and toenails that do not reach the tips of the digits until the ninth month of development. IX. SWEAT GLANDS Two types: Figure 16. [A,B] Developping mammary gland at the third and eight - Eccrine months, [C] Positions of accessory nipples - blue line, mammary line - Apocrine PREPARED BY: CMED 1D Page 10 of 12  (001) EMBRYONIC DEVELOPMENT OF THE SKELETAL AND MUSCULAR SYSTEM. DR. PABLO QUEDADO | 12/01/20 XI. CLINICAL CORRELATIONS A. PIGMENTARY DISORDERS Classified as diseases of melanocyte development, function, and survival. 1. ABNORMALITIES OF MELANOCYTE FUNCTION: Figure 18. Child with hypertrochosis a. PIEBALDISM - patchy absence of hair and skin pigment b. WAARDENBURG SYNDROME (WS) C. MAMMARY GLAND ABNORMALITIES - Which feature patches of white skin and hair, 1. POLYTHELIA heterochromia irides (eyes of different colors), white - Is a condition in which accessory nipples have formed patches of skin, and deafness. resulting from the persistence of fragments of the - defects arise because of faulty migration or mammary line. proliferation of neural crest cells - Accessory nipples may develop anywhere along the c. ALBINISM original mammary line but usually appear in the axillary - characterized by globally reduced or absent region. pigmentation in the skin, hair, and eyes d. VITILIGO - results from a loss of melanocytes due to an autoimmune disorder. - patchy loss of pigment from affected areas, including the skin and overlying hair and the oral mucosa - also associated with other autoimmune diseases, particularly of the thyroid 2. KERATINIZATION OF SKIN A. ICHTHYOSIS - excessive keratinization of the skin - characteristic of a group of hereditary disorders that Figure 19. Child with bilateral polythelia (supplementary nipples) are usually inherited as an autosomal recessive trait 2. POLYMASTIA but may also be X-linked - Occurs when a remnant of the mammary line develops - In severe cases, it may result in a grotesque into a complete breast. appearance, as in the case of a harlequin fetus 3. INVERTED NIPPLE - Is a condition in which the lactiferous ducts open into the original epithelial pit that has failed to evert TEST YOUR KNOWLEDGE 1. The superficial layer of the skin is developed from this germ layer. A.Mesoderm B.ectoderm c. endoderm Figure 17. Ichthyosis in a harlequin fetus. D. None of the above B. ABNORMALITIES OF HAIR DISTRIBUTION 2. The first hair that appears and is later replaced by coarser 1. HYPERTRICHOSIS hairs arising from new hair follicles. - excessive hairiness 3. It is a condition characterized by globally reduced or absent - caused by an unusual abundance of hair follicles pigmentation in the skin, hair, and eyes. - may be localized to certain areas of the body, A. Vitiligo especially the lower lumbar region covering a spina B. Albinism bifida occulta defect or may cover the entire body C. Piebaldism 2. ATRICHIA D. lchthyosis - the congenital absence of hair, is usually associated with abnormalities of other ectodermal 4. Which layer of the epidermis is responsible for the production derivatives, such as teeth and nails. of new cells? A. Spinous layer B. Granular layer C. Horny layer D. Basal layer PREPARED BY: CMED 1D Page 11 of 12  (001) EMBRYONIC DEVELOPMENT OF THE SKELETAL AND MUSCULAR SYSTEM. DR. PABLO QUEDADO | 12/01/20 5. This condition occurs when a remnant of the mammary line develops into a complete breast. A. Polythelia B. Polymasthia C. Inverted Nipples D. All of the Above 6. Which of the following develop from epidermal proliferations? A. Sebaceous glands B. Sweat glands C. Mammary glands D. All of the Above 7. The congenital absence of hair A. Hypertrichosis B. Ichthyosis C. Atrichosis D. None of the Above REFFERENCES PPT - Doc Pablo Quedado Langman's Medical Embryology by T.W. Sadler. 14th EDITION. Chapter 10: Axial Skeleton. Pages 147-159. Langman's Medical Embryology by T.W. Sadler. 14th EDITION. Chapter 12: Limbs. Pages 167-178 Langman's Medical Embryology by T.W. Sadler. 14th EDITION. Chapter 21: Integumentary System. Pages 370-375 ANSWER KEYS BABBCABCAB 1.Osteogeneses imperfecta 2.Limb defect 3. Synpolydactyly 4.Amelia 5.Hand-foot genital syndrome // T T T F T // 7th 5th end of 4th 7th 6th B Lanugo hair B D B D C PREPARED BY: CMED 1D Page 12 of 12