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Embryology of The Axial Skeleton

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Gal De León
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22 views13 pages

Embryology of The Axial Skeleton

Uploaded by

Gal De León
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© © All Rights Reserved
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The Axial Skeleton The ai seen nds the dle a tumn, ribs, and sternum In genera, syslem develops from. paraxial and iste seo cpeualibesoory 2s somitomeres in the ead eon and somites from the occipital region caudal Somitsdilr- ent ino 2 venta pat he setae, and a dorsols the nd of hah Wed seo else: ooo aetna een “issue, caled mesenchyme, or embryonic connec- tie. isan and to differe not sclerotome but occurs also in the of the me- soderm of the body wall. This layer of mesoderm limbs, cls id region also differentiate into et participate of the face and skull. The remainder of the skull is derived from. ‘cpt somilesand noma bagel such as ‘volitondediedl xcaivann the dermis diferentes died nto bone, pro: «x85 known a5 intramembranous ossification (Fig, 102). n_ most bones, however, including Which in turn beeome ossified by ossification (Fg. 103). The following paragraphs discuss development of the most important bony siructures and some oftheir abnormalities. m SKULL “The skull can be divided into ee ase Dorsomedial Neural tube Dermatome Neural olds Yontolatera muscle cals = lnta embryonic — S. cautly A Venta B somite Wall Norochona Sclorctome Dorsal aorta FIGURE 10. Development ofthe somite. A. Paraxial mesoderm cells ae arranged around a small cavity. B.AS2 result of further cifferentiation, cellsin the ventromedial wall ase tl enthela arrangement and became mes enchymal.Colectivaly, they are called the scleretome. Cells in tne ventrolateral and dorsomedial regions form ‘muscle eels and also migrate beneath the remaining dorsal epithelium (the dermatome) to form the myatome. ar ss Part 2 Systems-Based Embryology Parietal bone Occipital bone Cervical vertebrae Mandible FIGURE 10.2 Skull bones ofa 3-month-old fetus shaw the soread of bane spicules from primary ossification, centers in the flat bones ofthe sk Secondary ‘ossification center chondrocytes A B c FIGURE 10.3 Endochondral bone formation. A. Mesenchyme cells begin to condense and diferetiate ito chondrocytes. B. chondrocytes form a cartiaginous model ofthe prospective bone. €,D. Blood vessls vade the center of the cartlaginous mode, bringing osteoblasts [black cells) and restricting arelferting chondrocyte eel ta the ends [epphyses) of te bones. chondrocytes toward the shaft side (saphysis) une ergo hypert-ophy ae apoptoss as they mreralize the surrounding mate Osteoblass bind ta the miner- alized matrix and deposit bone matrices. Later, as blood vessels invade he epinhyses, secondary ossification centers frm. Gronth ofthe bones is maintained by paiferation of cnandrocytes in the growth plates, Chapter 10 - The Axial Skeleton gone Monat [eel angst FIGURE 10.4 Séeletal structures of the head and face, Mesenchyme for these structuresis derived from neu ral crest [bivel, paraxial mesoderm [somites an so- ‘mitomeres} red, and lateral plate mesoderm [yellow Frontal ot metope suture Frontal Anterolateral ‘or sphenaial ‘ontanole FIGURE 10.5 Skull of anewborn, seen Irom above (A] and the right side (B). Note the anterior ané posterior fontanelles and sutures. The posterior fontanelle closes about 3 months after birth; the anterior fontanelle closes around the middle af the second year. Many ofthe sutures disappear during adult ite art 2 Systems-Based Embryelogy FIGURE 10.6 Dorsal view of the chondracranium, or base ofthe skull. the acuit snowing bores formed by endochondral ossification. Bones that form ros tral to the rastal half ofthe sella turcica arise from neural crest and constitute the prechordal infront ‘of the natochord) chondracranium blue). Those Forming posterior to this landmark arise from para xial mesoderm (chordal chandrocranium) (red) terior fontanelle may give FIGURE 10,7 Lateral view of tne head and neck region of ‘an older fetus, showing deriva tives ofthe arch cartilages par- ligating in formation of bones ofthe face. Cartilaginous Neurocranium or Chondrocranium ‘The cartilaginous neurocr which ends the center (igs 103 an 00) Viscerocranium {emparal Bone catlage th PrOEE) contains the Meckel Mesenchyme around: the Meckel.car- tilage condenses and ossifies by intramembra- nous ossification to give rise to the mandible. The Meckel cartilage sphenomandibular ligament. ‘The dorsal tip of the mandibular process, along with that of the second pharyngeal. arch, later gives rise to the incus, the (ig, 107) ssification of the three ossicles a in the Chapter 10 - The Axial Skeleton become lly Ossie) Mesenchyme for forma tion of the bones of the face is derived from neu- ral crest cells, including the nasal and lacrimal bones (Fig. 10.4), ‘Abfirs ith thy [his appearance is caused by. Col eee Craniofacial Defects and Skeletal Dysplasias ‘Neural Crest Cells Neural crest cells originating in the neuroecto- derm form the facial skeleton and part of the skull, These cells aiso constitute a vulnerable population as they leave the neuroectoderm; theyare often a target for teratagens. Therefore, itis not surprising that craniofacial abnormali- ties are common birth defects (see Chapter 17) Cranioschisis Insome cases, the cranial vault fails to form era~ nioschisis), and brain tissue exposes to amniot- ic fluid degenerates, resulting in anencephaly. FIGURE 10.8 A, Child wit Cranioschisis is caused by failure ofthe cranial neuropore to close (Fig. 1.84). Chien with such Severe skull and brain defects cannot sur- vive. Children with relatively small defects in the skil through which meninges and/or brain tissue herniate (cranial meningocele and me- ringoencephalocele, respectively) (Fig. 10.88) may be treated successfully. In such cases, the extent of neurological deficits depends on the ‘amount of damege to brein tissue. Craniosynostosis Another important category of cranial abnor- maltes is caused by premature closure of one ‘or more sutures. These abnormalities are col- lectively known as craniosynestosis, which anencephaly, Cranial neural folds fal to elevate and fuse, leaving the cranial rneuropore open. The skull never forms, and brain tissue degenerates. B, Patient with meningocele. This rather common abnormality may be successfully repaired Part 2 Systems-Based Embryology ‘occurs in 1 in 2,500 births and is a feature of more than 100 genetic syndromes. Regula~ tion of suture growth and closure is not well understood but may involve interactions be~ tween neural crest-mesoderm cell boundaries. For example, crest calls form the frontal bones, Whereas paraxial mesoderm forms the parietal bones and the loose mesenchyme in the car- onal sutures. Also, crest cells migrate between the parietal bones and form the first part of the sagittal suture. Molecular signaling at these boundaries regulates cell proliferation and differentiation. For example, EFNB? encodes ephrin-B1, a ligand for Eph receptors that causes cells to repel each other, a kind of an- tiadhesive activity and important for prevent- ing premature suture closure, Loss of function ‘mutations in EFNBY couses craniofrontonasal syndrome, characterized by coronal suture synostosis and hypertelorism. Proliferation of ‘neural crest cells in the frontal bones is regulat- ‘ed in partby the transcription factors MSx2 and TWIST! that act cooperatively in parallel path- ways. Mutations in MSX2 cause Beston-type craniesynestesis that can affect a number of sutures, whereas mutations in TWISTI cause Saethre-Chotzen syndrome, characterized by Coronal sulure synostosis and polydactyly Fibroblast growth factors (FGFs) anc fibro- blast growth factor receptors (FGFRs) play im portant roles in most of skeletal development. There are many members of the FGF family and their receptors. Together, they regulate cellular events, including proliferation, differentation, ‘and migration. Signaling is meciated by the recep tors, which are transmembrane tyrosine kinase receptors, each of which has three extracellu- lar immunoglobulin domains, a transmembrane segment, and 2 cytoplasmic tyrosine kinase domain. FGFRI and FGFR2 ere coexpressed in prebone and precartilage regions, including cra- hiofacial structures; FGFR3 is expressed in the cartilage growth plates of long bones and in the ‘cisitl region. In general, FGFR2 increases pro- liferation, and FGFR! promotes osteogenic aiffer- entiation, whereas the role of FGFR3 is unclear. Mutations in these receptors, which often in- volve only a single amino acid substitution, nave been linked to specific types of eraniosynastosis, (GGFR, FGFR2, and FGFR3) and several forms of skeletal dysplasia (FGFR3) (Table 101 The shape of the skull depends on which of the sutures closes prematurely, Early closure of the sagittal suture (57% of cases) results in frontal and occipital expansion, and the skull becomes long and narrow {scaphocephaly] (Fig, 1.9), Premature closure of the coronal su- tures [20% to 25% of cases} results in a short skull called brachycephaly (Fig. 10:104). If the coronal sutures close prematurely on one side only, then the result isan asymmetric flattening of the skull called plagiocephaly [Fig. 10.108.0). By far, the most common causes of cra- niosynostosis are genetic (Table 102]. Other ‘causes include, vitamin D deficiency; exposure to teratogens, including, diphenylhydantoin, retinoids, valproic acid, methotrexate, and cy- clophosphamide; and intrauterine factors that constrain the fetus, such as oligohydramnios ‘and multiple birth pregnancies. ‘Skeletal Dysplasias ‘Achondroplasia (ACH), the most common form of skeletal dysplasia (1/20,000 live births}, ori- rmariy affects the lang bones (Fig. 10714) Other skeletal defects include a large skull (megalo- cephaly] with a small midface (Fig. 1071}, short fingers, and accentuated spinal curvature. ACHis inherited as an autosomal dominant, and 90% of ‘aes appear sporadically due to new mutations. Thanatophoric dysplasia is the most com- ‘mon neonatal lethal form of skeletal dysplasia {0/40,000 live births}. There are two types: both are autosomal dominant. Type lis cheracterized by short, curved femurs with or without clover- leaf skull type Il individuals have straight, el- atively long femurs and severe cloverieat skull ‘caused by craniosynostosis (Fig, 10:2). Another term for clovereaf skulls Kleeblattsehadel. It ‘occurs when all of the sutures close prema- turely, resulting in the brain growing through the anterior and sphenoid fontanelles. Hypochondroplasia, another autosomal dominant form of skeletal dysplasia, appears to bbe milder type of ACH. Common to all of these forms of skeletal dysplasias are mutations in FFGFR3 causing abnormal endochondral bone formation so that grow of the long bones and the base ofthe skull are adversely affected Generalized Skeletal Dysplasia Cleldecranial dysostosis is an example of a generalized dysplasia of osseus and dental tissues that is characterized by late closure of the fontanelles and decreased mineralization of the cranial sutures resulting in bossing [en largement) ofthe frontal, parietal, and occipital bones (Fig, 10.13). Other parts of the skeleton are affected as well, and oftentimes, the clavi- cles are underdeveloped or missing. Gene Farr! FoFR2 Fores sx2 rust HOxANS Hoxoi3 Tex COLIATand cOLIAZ Fibrin [Fan Chapter 10 - The Axial Skeleton Sire Chromosome Bol toge6 p16 5935 1921 p15 2q31 12q24 Tat and Tq21 15q15-21 ‘Abnormality Peiffer syndrome Peiffer syndrome Apert syndrome Jackson-Weiss syndrome Crouzon syndrome Achondroplasia (ACH) Thanatophoric Ayspasia (type) Thanatophoric dysplasia (typeI) Hypochondroplasia Boston-type craniosynostosis Saethre-Chotzen syndrome Hand-foot genital syndrome Synpolydactyly Upper limb and heart defects Limb defects, biue sclera Marfan syndrome Phenotype Craniosynostosis, broad great toes and thumbs, cloverleaf skul underdeveloped face Same Craniosynostosis, underdeveloped face, symmetric syndactyiy of hands and feet Craniosynostosis, underdeveloped face, foot anomalies, hands usuelly spared Craniosynostosis, underdeveloped face, ‘no foot or hand defects Short-limb dwarfism, underdeveloped face Curved short femurs, with or without Cloverieaf skull Relatively long femurs, severe cloveriegt skull Milder form of ACH with normal craniofacial features Craniosynostosis Craniosynostosis, midfacial hypoplasia, left palate, vertebral anomalies, hand and foot abnormalities ‘Small, hort digits, divided uterus, hypospadias Fused, multiple digits Digit defects, absent radius, limb bone hypoplasia, arial and ventricular septal defects, conduction abnormalities Shortening, bowing, and hypomineralization of the long bones, blue sclera Long limbs and face, sternal defects (pectus excavatum and carinatum, lation and dissection of the ascending aorta, lens dislocation Part 2 - Systems-Based Embryology FIGURE 10.9 Craniosynostosis in volving the sagital suture. Child with scephacephaly caused by early closure ofthe sagittal suture Note the long narrow shape of the head with prominent frontal and occipital regions. B,C. Computed tomography [CT] scans of the skull showing the long narrow shape af the head with bassing ofthe fran- lal andoccipital regions (8) cused by premature closure of the sagi- tel suture () FIGURE 10:10 Craniosynostosis involving the coronal sutures. A. Child with brachyceahaly caused by early closure of both coronal sutures. Note the tall shape ofthe skull with flattened frontal and occioital regions. B Child with plagiocephaly resulting from premature closure of te coronal suture on one side of, the skull. Computed tomography [CT] scar ofthe skull showing alagiocephaly resulting fram premature closure ofthe coronal suture on ane side, Chapter 10 - The Axial Skeleton URES} FIGURE 10.11 A. Nine-year-old child with achondroplasia (ACH] showing a large head, short extremities, ‘short fingers, and protruding abdomen. head and miafacial hypoolasia, FIGURE 10:12 Patient with cloverleaf skull char- acteristic of thanetophoric dwerlism type I. The shape ofthe skull results from abnormal growth of the cranial base, caused by a mutation in FGFR3, followed by craniosynastosis, The sagital, coro ral, and lambdold sutures are commonly valves. Lateral view of the patient's head showing a prominent fore- FIGURE 10.13 Child with cleidocrarial dysostosis with generalized skeletal dysplasias. One charac teristic ofthe condition is delayed closure of the fontanelles and decreased mineralization of the ‘cranial sulures, such thatthe head appears larger ‘due to bossing of the frontal, parietal and occipi- tal bones. Other parts of the skeleton are affected {3s well, and often, the clavicles are underdevel- ‘oped or missing, as inthis case. Part 2 - Systems-Based Embryology ‘Acromegaly ‘Acromegaly is caused by congenital hyperpi- tuitarism and excessive production of growth hormone. Its characterized by disproportional enlargement of the face, hands, and fect. Sometimes, it causes more symmetrical ex- cessive grawth and gigantism. Microcephaly Microcephaly is usually an abnormality in which the brain fails to grow and, as a result, the skull fails to expand (Fig. 10.14). Many chi dren with microcephaly are severely intellectu- ally disabled, FIGURE 10.14 Child with microcephaly showing 2 small head due to the fact that the brain failed to graw to its normal size. One cause for this ab normality is exposure to alcohol in utero. In most cases, microcephaly is associated with significant intellectual dsabilties VERTEBRAE AND THE VERTEBRAL COLUMN of (Fig. 10.15), ts around Dorsomedial Neural tube muscle col Transverse process Dermatome Ventoiatera! muses ces Intra ‘embryonic aly 7 Sclortome Dorsal aorta, FIGURE 10.15 A. Cross section showing the developing regions ofa somite, Sclerotome cells are dispersing ta migrate around the neural tube and notochord to cantribute ta vertebral formation. B. Example of atypical vertebra showing is various components, Chapter 10 - The Axial Skeleton RED Nucous Inlervortbral Intervertebral Neon Palpasus ase — Vero Intrsegmertal Procatlag mosonenyme vertebral Intersegmertal ‘teres, Tranovo Spinal process rewes Annus Somos ‘orosus (sceroteme) A FIGURE 10.16 Formation ofthe vertebral columa at various stages of development, A. At the fourth week of development, sclerotomic segments are separated by less dense intersegmental Lssue. Note the position of the myatomes, intersegmental arteries, and segmental nerves. B Proliferation ofthe caudal haf of one sclerotome proceeds Into the Intersegmental mesenchyme and cranial half af the subjacent sclerotome [arrows]. Note the appearance of the intervertebral discs. €, Vertebrae are formed by the upper and lower halves of two successive sclerolomes and the intersegmental tissue. Myotomes bridge the intervertebral discs and, therefore, can move the vertebral column, (arrows in Fig, formed from fone somite and the. (Fig 10.168), though the notochord represses felis eedee ded Vertebral Defects missing, a cause of scoliosis (lateral curving The process of formation and rearrang the spine). Aiso, the number of vertebrae ment of segmental sclerotomes into defini- is frequently more or less than the norm. In tive vertebrae is complicated, and itis faidy Klippel-Feil sequence, the cervical vertebrae common to have two successive vertebrae are fused causing reduced mobility and a fuse asymmetrically or have half a vertebra short neck Part 2 - Systems-Based Embryology One of the most serious vertebral defects is the result of imperfect fusion or nonunion fof the vertebral arches. Such an abnormality, known as cleft vertebra (spina bifida), may involve only the bony vertebral arcines, leaving the spinal cord intact. In these cases, the bony defect is covered by skin, and no neurological deficits occur (spina bifida occulta). A more severe abnormality is spina bifida cystica, in which the neural tube fails to close, verte- bral arches fail to form, and neural tissue is exposed, Any neurological deficits depend on the level and extent ofthe lesion (Fig. 1017 This defect, which occurs in per 2.500 births, may be prevented, in many cases, by providing mothers with folic acid prior to conception (see Chapter 6, 73], Spina bifida con be detected prenatally by ultrasound, and f neural tissue i exposed, armiocentesis can detect elevated levels of «-fetoprotein in the amniotic fluid. [For the various types of spina bifida, see Fig. 61 p73) FIGURE 10.17 A, Ultrasound scan of a 26-week-old fetus with spina bifida in the lumbosacral region Ultrasound scan showing the skul of a 26-week-old fetus with spina bifida. Because of the shape of the skull, the image is called the “lemon sign” which occurs in some ofthese cases ands due to the brain being pulled caudally, changing the shape af the head (see Armold-Chiari malformation, p.323) RIBS AND STERNUM

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