Brownian Motion
Section 4.3: Estimating rates using maximum likelihood
(see Chapter 12). Neural crest cells in the head region also differentiate into mesenchyme and participate in formation of bones of the face and skull. The remainder of the skull is derived from occipital somites and somito-meres. In some bones, such as the flat bones of the skull, mesenchyme in the dermis differ-entiates directly into bone, a process known as intramembranous ossifi cation (Fig. 10.2).
In most bones, however, including the base of the skull and the limbs, mesenchymal cells first give rise to hyaline cartilage models, which in turn become ossified by endochon-dral ossifi cation (Fig. 10.3). The following paragraphs discuss development of the most important bony structures and some of their abnormalities.
SKULL
The skull can be divided into two parts: the neurocranium, which forms a protective case around the brain, and the viscerocranium, which forms the skeleton of the face.
T
he axial skeleton includes the skull, vertebral column, ribs, and sternum. In general, the skeletal system develops from paraxial and lateral plate (parietal layer) mesoderm and from neural crest. Paraxial mesoderm forms a segmented series of tissue blocks on each side of the neural tube, known as somitomeres in the head region and somites from the occipital region caudally. Somites differentiate into a ventromedial part, the sclerotome, and a dorsolateral part, the dermomyotome. At the end of the fourth week, sclerotome cells become polymorphous and form loosely organized tissue, called mesenchyme, or embryonic connective tissue (Fig. 10.1). It is char-acteristic for mesenchymal cells to migrate and to differentiate in many ways. They may become fi broblasts, chondroblasts, or osteoblasts (bone-forming cells).The bone-forming capacity of mesen-chyme is not restricted to cells of the sclero-tome, but occurs also in the parietal layer of the lateral plate mesoderm of the body wall.
This layer of mesoderm forms bones of the pelvic and shoulder girdles, limbs, and sternum
A B
Neural groove
Ventral
somite wall Notochord
Intra-embryonic
cavity
Sclerotome
Neural tube
Dorsal aorta Dorsomedial muscle cells Dermatome Ventrolateral muscle cells
Figure 10.1 Development of the somite. 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 become mesenchymal.
Collectively, they are called the sclerotome. Cells in the ventrolateral and dorsomedial regions form muscle cells and also migrate beneath the remaining dorsal epithelium (the dermatome) to form the myotome.
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134 Part 1I Systems-Based Embryology
Parietal bone
Nasal bone Frontal bone
Bone spicules
Occipital bone
Cervical vertebrae
Mandible Maxilla
Figure 10.2 Skull bones of a 3-month-old fetus show the spread of bone spicules from primary ossifi cation centers in the fl at bones of the skull.
A B C D
Cartilage Osteoblasts
Bone
Growth plate Proliferating
chondrocytes
Secondary ossification center
Mesenchyme
Figure 10.3 Endochondral bone formation. A. Mesenchyme cells begin to condense and differentiate into chondrocytes.
B. Chondrocytes form a cartilaginous model of the prospective bone. C,D. Blood vessels invade the center of the cartilagi-nous model, bringing osteoblasts (black cells) and restricting proliferating chondrocytic cells to the ends (epiphyses) of the bones. Chondrocytes toward the shaft side (diaphysis) undergo hypertrophy and apoptosis as they mineralize the surround-ing matrix. Osteoblasts bind to the mineralized matrix and deposit bone matrices. Later, as blood vessels invade the epiphy-ses, secondary ossifi cation centers form. Growth of the bones is maintained by proliferation of chondrocytes in the growth plates.
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Chapter 10 The Axial Skeleton 135
centers toward the periphery (Fig. 10.2). With further growth during fetal and postnatal life, membranous bones enlarge by apposition of new layers on the outer surface and by simultaneous osteoclastic resorption from the inside.
Newborn Skull
At birth, the fl at bones of the skull are separated from each other by narrow seams of connective tissue, the sutures, which are also derived from two sources: neural crest cells (sagittal suture) and paraxial mesoderm (coronal suture). At points where more than two bones meet, sutures are wide and are called fontanelles (Fig. 10.5). The most prominent of these is the anterior fonta-nelle, which is found where the two parietal and two frontal bones meet. Sutures and fontanelles allow the bones of the skull to overlap (mold-ing) during birth. Soon after birth, membranous bones move back to their original positions, and the skull appears large and round. In fact, the size of the vault is large compared with the small facial region (Fig. 10.5B).
Several sutures and fontanelles remain mem-branous for a considerable time after birth. The bones of the vault continue to grow after birth, mainly because the brain grows. Although a 5- to 7-year-old child has nearly all of his or her cranial capacity, some sutures remain open until adulthood. In the fi rst few years after birth, pal-pation of the anterior fontanelle may give valu-able information as to whether ossifi cation of the skull is proceeding normally and whether Neurocranium
The neurocranium is most conveniently divided into two portions: (1) the membranous part, con-sisting of fl at bones, which surround the brain as a vault, and (2) the cartilaginous part, or chondrocranium, which forms bones of the base of the skull.
Membranous Neurocranium
The membranous portion of the skull is derived from neural crest cells and paraxial mesoderm as indicated in Figure 10.4. Mesenchyme from these two sources invests the brain and under-goes intramembranous ossifi cation. The result is formation of a number of fl at, membra-nous bones that are characterized by the presence of needle-like bone spicules. These spicules progressively radiate from primary ossifi cation
Nasal Lacrimal Zygomatic Maxilla Incisive Mandible
Sphen Sq. temp.
Frontal Parietal
Pet. temp.
Occipitals Hyoids
Laryngeals
Figure 10.4 Skeletal structures of the head and face.
Mesenchyme for these structures is derived from neural crest (blue), paraxial mesoderm (somites and somitomeres) (red), and lateral plate mesoderm (yellow).
Frontal eminence
Parietal eminence
Maxilla Mandible Sagittal
suture Coronal
suture
A
B Frontal or
metopic suture
Occipital bone
Lambdoid suture Anterior fontanelle
Anterolateral or sphenoidal fontanelle
Posterolateral or mastoid
fontanelle Posterior
fontanelle
Figure 10.5 Skull of a newborn, seen from above A and the right side B. Note the anterior and posterior fontanelles and sutures. The posterior fontanelle closes about 3 months after birth; the anterior fontanelle closes around the middle of the second year. Many of the sutures disappear during adult life.
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Ethmoid Lesser wing of sphenoid Greater wing
of sphenoid Pituitary
fossa Body of sphenoid
Base of occipital bone Petrous
bone Cut edge of the skull
Foramen magnum
Figure 10.6 Dorsal view of the chondrocranium, or base of the skull, in the adult showing bones formed by endochondral ossifi cation. Bones that form rostral to the rostral half of the sella turcica arise from neural crest and constitute the prechordal (in front of the notochord) chondrocranium (blue). Those forming posterior to this landmark arise from paraxial mesoderm (chordal chondro-cranium) (red).
Squamous temporal bone
Incus
Stapes Styloid process Stylohyoid
ligament Cricoid
cartilage Meckel’s
cartilage
Thyroid cartilage Hyoid bone Mandible Maxilla Zygomatic
bone Zygomatic
process
Figure 10.7 Lateral view of the head and neck region of an older fetus, showing derivatives of the arch cartilages partici-pating in formation of bones of the face.
Cartilaginous Neurocranium or Chondrocranium The cartilaginous neurocranium or chondrocra-nium of the skull initially consists of a number of separate cartilages. Those that lie in front of the rostral limit of the notochord, which ends at the level of the pituitary gland in the center of the sella turcica, are derived from neural crest cells. They form the prechordal chondrocra-nium. Those that lie posterior to this limit arise from occipital sclerotomes formed by paraxial mesoderm and form the chordal chondro-cranium. The base of the skull is formed when these cartilages fuse and ossify by endochondral ossifi cation (Figs. 10.3 and 10.6).
Viscerocranium
The viscerocranium, which consists of the bones of the face, is formed mainly from the fi rst two pharyngeal arches (see Chapter 17). The fi rst arch gives rise to a dorsal portion, the maxil-lary process, which extends forward beneath the region of the eye and gives rise to the max-illa, the zygomatic bone, and part of the temporal bone (Fig. 10.7). The ventral portion, the mandibular process, contains the Meckel cartilage. Mesenchyme around the Meckel car-tilage condenses and ossifi es by intramembra-nous ossifi cation to give rise to the mandible.
The Meckel cartilage disappears except in the sphenomandibular ligament. The dorsal tip of the mandibular process, along with that of the second pharyngeal arch, later gives rise to the intracranial pressure is normal. In most cases,
the anterior fontanelle closes by 18 months of age, and the posterior fontanelle closes by 1 to 2 months of age.
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A B
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C B
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A B
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undergoes a process called resegmentation.
Resegmentation occurs when the caudal half of each sclerotome grows into and fuses with the cephalic half of each subjacent sclerotome (arrows in Fig. 10.16A,B). Thus, each vertebra is formed from the combination of the caudal half of one somite and the cranial half of its neigh-bor. Patterning of the shapes of the different vertebrae is regulated by HOX genes.
Mesenchymal cells between cephalic and cau-dal parts of the original sclerotome segment do not proliferate but fi ll the space between two precar-tilaginous vertebral bodies. In this way, they con-tribute to formation of the intervertebral disc (Fig. 10.16B). Although the notochord regresses VERTEBRAE AND THE VERTEBRAL
COLUMN
Vertebrae form from the sclerotome portions of the somites, which are derived from par-axial mesoderm (Fig. 10.15A). A typical verte-bra consists of a verteverte-bral arch and foramen (through which the spinal cord passes), a body, transverse processes, and usually a spinous process (Fig. 10.15B). During the fourth week, sclerotome cells migrate around the spinal cord and notochord to merge with cells from the opposing somite on the other side of the neu-ral tube (Fig. 10.15A). As development contin-ues, the sclerotome portion of each somite also
Transverse process
Vertebral body Spinous process
Lamina Pedicle
Vertebral foramen
Vertebral arch
B
Intra-embryonic cavity
Sclerotome
Neural tube
Dorsal aorta Dorsomedial muscle cells Dermatome Ventrolateral muscle cells
A
Figure 10.15 A. Cross section showing the developing regions of a somite. Sclerotome cells are dispersing to migrate around the neural tube and notochord to contribute to vertebral formation. B. Example of a typical vertebra showing its various components.
Notochord Nucleus pulposus and
intervertebral disc
Intervertebral disc
Sclerotome segment Nerve Artery Intersegmental
mesenchyme
Transverse process Annulus fibrosus
Precartilagi-nous vertebral Myotome body
A B C
Figure 10.16 Formation of the vertebral column at various stages of development. A. At the fourth week of devel-opment, sclerotomic segments are separated by less dense intersegmental tissue. Note the position of the myotomes, intersegmental arteries, and segmental nerves. B. Proliferation of the caudal half of one sclerotome proceeds into the inter-segmental mesenchyme and cranial half of the subjacent sclerotome (arrows). Note the appearance of the intervertebral discs. C. Vertebrae are formed by the upper and lower halves of two successive sclerotomes and the intersegmental tissue.
Myotomes bridge the intervertebral discs, and therefore, can move the vertebral column.
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A B
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W
ith the exception of some smooth muscle tissue (see later), the muscu-lar system develops from the meso-dermal germ layer and consists of skeletal, smooth, and cardiac muscle. Skeletal muscle is derived from paraxial mesoderm, which forms somites from the occipital to the sacral regions and somitomeres in the head. Smooth muscle differentiates from visceral splanchnic mesoderm surrounding the gut and its deriva-tives and from ectoderm (pupillary, mammary gland, and sweat gland muscles). Cardiac muscle is derived from visceral splanchnic mesoderm surrounding the heart tube.STRIATED SKELETAL MUSCULATURE
Head musculature (see Chapter 17) is derived from seven somitomeres, which are par-tially segmented whorls of mesenchymal cells derived from paraxial mesoderm (see Chapter 6, p. 72). Musculature of the axial skeleton, body wall, and limbs is derived from somites, which initially form as somitomeres and extend from the occipital region to the tail bud. Immediately after segmentation, these somitomeres undergo a process of epitheliza-tion and form a “ball” of epithelial cells with a small cavity in the center (Fig. 11.1A). The ventral region of each somite then becomes mesenchymal again and forms the sclero-tome (Fig. 11.1B–D), the bone-forming cells for the vertebrae and ribs. Cells in the upper region of the somite form the dermatome and two muscle-forming areas at the ventrolateral (VLL) and dorsomedial (DML) lips (or edges), respectively (Fig. 11.1B). Cells from these two areas migrate and proliferate to form progeni-tor muscle cells ventral to the dermatome, thereby forming the dermomyotome (Figs.
11.1B,C and 11.2). Some cells from the VLL region also migrate into the adjacent parietal layer of the lateral plate mesoderm (Fig. 11.1B).