Pharyngeal Apparatus, Face, and Neck

T he pharyngeal apparatus consists of pharyngeal arches, pouches, grooves, and membranes ( Fig. 9.1 ). These early embryonic structures contribute to the formation of the face and neck.

Pharyngeal Arches

The pharyngeal arches begin to develop early in the fourth week as neural crest cells migrate into the future head and neck regions (see Chapter 5 , Fig. 5.5 ). The first pair of arches, the primordial jaws, appears as surface elevations lateral to the developing pharynx (see Fig. 9.1 A and B ). Other arches soon appear as ridges on each side of the future head and neck regions (see Fig. 9.1 C and D ). By the end of the fourth week, four pairs of arches are visible externally (see Fig. 9.1 D ). The fifth and sixth arches are rudimentary and are not visible on the surface of the embryo. Sonic hedgehog (Shh) and homeobox gene Dlx2 signaling play an important role in the formation and patterning (anterior-posterior and dorsoventral) of the pharyngeal arches.

The pharyngeal arches are separated by pharyngeal grooves (clefts). Like the arches, the grooves are numbered in a craniocaudal sequence (see Fig. 9.1 D ). The first arch separates into the maxillary and mandibular prominences ( Fig. 9.2 ; see Fig. 9.1 E ). The maxillary prominence forms the maxilla, zygomatic bone, and a portion of the vomer bone. The mandibular prominence forms the mandible and squamous temporal bone. Along with the third arch, the second arch (hyoid arch) contributes to the formation of the hyoid bone.

Fig. 9.2, Photograph of a stage 13, 4.5-week human embryo.

The arches support the lateral walls of the primordial pharynx , which is derived from the cranial part of the foregut. The stomodeum (primordial mouth) initially appears as a slight depression of the surface ectoderm (see Fig. 9.1 D and G ). It is separated from the cavity of the primordial pharynx by a bilaminar membrane, the oropharyngeal membrane , which is composed of ectoderm externally and endoderm internally (see Fig. 9.1 E and F ). This membrane ruptures at approximately 26 days, bringing the pharynx and foregut in communication with the amniotic cavity. Persistence of the oropharyngeal membrane may result in orofacial defects. The ectodermal lining of the first arch forms the oral epithelium.

Pharyngeal Arch Components

Each arch consists of a core of mesenchyme (embryonic connective tissue) and is covered externally by ectoderm and internally by endoderm (see Fig. 9.1 H and I ). Originally, the mesenchyme is derived during the third week from mesoderm. During the fourth week, most of the mesenchyme is derived from neural crest cells that migrate into the arches. Migration of the multipotent neural crest stem cells into the arches and their differentiation into mesenchyme produce the maxillary and mandibular prominences (see Fig. 9.2 ) in addition to all connective tissue, including the dermis (layer of skin) and smooth muscle.

Coincident with the immigration of neural crest cells, myogenic mesoderm from paraxial regions moves into each arch, forming a central core of muscle primordium . Endothelial cells in the arches are derived from the lateral mesoderm and invasive angioblasts (cells that differentiate into blood vessel endothelium) that move into the arches. The endothelium of the pharyngeal arches 3 to 6 is derived from endothelial progenitors of the second heart field. The pharyngeal endoderm plays an essential role in regulating the development of the arches.

A typical pharyngeal arch contains several structures:

An artery arises from the truncus arteriosus of the primordial heart ( Fig. 9.3 B ) and passes around the primordial pharynx to enter the dorsal aorta.
A cartilaginous rod forms the skeleton of the arch.
A muscular component differentiates into muscles in the head and neck.
Sensory and motor nerves supply the mucosa (tissue lining) and muscles derived from each arch. The nerves that grow into the arches are derived from neuroectoderm of the primordial brain.

Fate of Pharyngeal Arches

The arches contribute extensively to the formation of the face, nasal cavities, mouth, larynx, pharynx, and neck (see Figs. 9.3 and 9.25 ). During the fifth week, the second arch enlarges and overgrows the third and fourth arches, forming an ectodermal depression, the cervical sinus (see Figs. 9.2 and 9.7 ). By the end of the seventh week, the second to fourth grooves and cervical sinus have disappeared, giving the neck a smooth contour.

Derivatives of Pharyngeal Arch Cartilages

The dorsal end of the first arch cartilage (Meckel cartilage) is closely related to the developing ear. Early in development, small nodules break away from the proximal part of the cartilage and form two of the middle ear bones, the malleus and incus ( Fig. 9.4 and Table 9.1 ). The middle part of the cartilage regresses, but its perichondrium (connective tissue membrane around cartilage) forms the anterior ligament of malleus and sphenomandibular ligament .

Fig. 9.4, A , Schematic lateral view of the head, neck, and thoracic regions of a 4-week embryo shows the location of the cartilages in the pharyngeal arches. B , Similar view of a 24-week fetus shows the derivatives of the arch cartilages. The mandible is formed by intramembranous ossification of mesenchymal tissue surrounding the first arch cartilage. The cartilage acts as a template for development of the mandible but does not contribute directly to its formation. Occasionally, ossification of the second arch cartilage may extend from the styloid process along the stylohyoid ligament. When this occurs, it may cause pain in the region of the palatine tonsil.

Table 9.1

Structures Derived From Pharyngeal Arch Components

Arches *	Cranial Nerves	Muscles	Skeletal Structures	Ligaments
First (mandibular)	Trigeminal (CN V) ^†	Muscles of mastication ^‡ Mylohyoid and anterior belly of digastric Tensor tympani Tensor veli palatini	Malleus Incus	Anterior ligament of malleus Sphenomandibular ligament
Second (hyoid)	Facial (CN VII)	Muscles of facial expression ^§ Stapedius Stylohyoid Posterior belly of digastric	Stapes Styloid process Upper part of body and lesser cornu of hyoid bone	Stylohyoid ligament
Third	Glossopharyngeal (CN IX)	Stylopharyngeus	Lower part of body and greater cornu of hyoid bone Superior cornu of the thyroid cartilage
Fourth and sixth ^¶	Superior laryngeal branch of vagus (CN X) Recurrent laryngeal branch of vagus (CN X)	Cricothyroid Levator veli palatini Constrictors of pharynx Intrinsic muscles of larynx Striated muscles of esophagus	Thyroid cartilage Cricoid cartilage Arytenoid cartilage Corniculate cartilage Cuneiform cartilage Body of Hyoid Bone

* The derivatives of the pharyngeal arch arteries are described in Fig. 13.38 in Chapter 13 .

† The ophthalmic division of the fifth cranial nerve (CN V) does not supply any pharyngeal arch components.

‡ Temporalis, masseter, medial, and lateral pterygoids.

§ Buccinator, auricularis, frontalis, platysma, orbicularis oris, and orbicularis oculi.

¶ The fifth pharyngeal arch is often absent. When present, it is rudimentary and usually has no recognizable cartilage bar. The cartilaginous components of the fourth and sixth arches fuse to form the cartilages of the larynx.

Ventral parts of the first arch cartilages form the horseshoe-shaped primordium of the mandible , and by keeping pace with its growth, they guide its early morphogenesis. Each half of the mandible forms lateral to and in close association with its cartilage. The first arch cartilage disappears as the mandible develops around it by intramembranous ossification (see Fig. 9.4 B ). Multiple signaling pathways involving the expression of homeobox genes ( BMP, PRRX1, and PRRX2 ), and fibroblast growth factors regulate the morphogenesis of the mandible.

An independent cartilage, the anlage (primordium) near the dorsal end of the second arch cartilage (Reichert cartilage), participates in ear development. It contributes to the formation of the stapes of the middle ear and the styloid process of the temporal bone (see Fig. 9.4 B ). The cartilage between the styloid process and hyoid bone regresses; its perichondrium forms the stylohyoid ligament . The ventral end of the second arch cartilage ossifies to form the hyoid lesser cornu (lesser horn; see Fig. 9.4 B ).

The third arch cartilage , located in the ventral part of the arch, ossifies to form the greater cornu of the hyoid bone and the superior cornu of the thyroid cartilage. The body of the hyoid bone is formed by the hypobranchial eminence (see Fig. 9.23 ).

The fourth and sixth arch cartilages fuse to form the laryngeal cartilages (see Fig. 9.4 B and Table 9.1 ), except for the epiglottis. The cartilage of the epiglottis develops from mesenchyme in the hypopharyngeal eminence (see Fig. 9.23 A ), a prominence in the floor of the embryonic pharynx that is derived from the third and fourth arches. The fifth arch , if present, is rudimentary and has no derivatives.

Derivatives of Pharyngeal Arch Muscles

The muscular components of the arches derived from unsegmented paraxial mesoderm and prechordal plate form various muscles in the head and neck. The musculature of the first arch forms the muscles of mastication and other muscles ( Fig. 9.5 ; see Table 9.1 ). The musculature of the second arch forms the stapedius , stylohyoid, posterior belly of digastric, auricular, and muscles of facial expression . The musculature of the third arch forms the stylopharyngeus . The musculature of the fourth arch forms the cricothyroid , levator veli palatini , and constrictors of pharynx . The musculature of the sixth arch forms the intrinsic muscles of the larynx.

Fig. 9.5, A , Lateral view of the head, neck, and thoracic regions of a 4-week embryo shows the muscles derived from the pharyngeal arches. The arrow shows the pathway taken by myoblasts from the occipital myotomes to form the tongue musculature. B , Sketch of the dissected head and neck regions of a 20-week fetus shows the muscles derived from the arches. Parts of the platysma and sternocleidomastoid muscles have been removed to show the deeper muscles. The myoblasts from the second arch migrate from the neck to the head, where they give rise to the muscles of facial expression. These muscles are supplied by the facial nerve (cranial nerve VII), which is the nerve of the second arch.

Derivatives of Pharyngeal Arch Nerves

Each arch is supplied by its own cranial nerve (CN). The special visceral efferent (branchial) components of these nerves supply muscles derived from the arches ( Fig. 9.6 , see Table 9.1 ). Because mesenchyme from the arches contributes to the dermis and mucous membranes of the head and neck, these areas are supplied with special visceral afferent nerves.

Fig. 9.6, A , Lateral view of the head, neck, and thoracic regions of a 4-week embryo shows the cranial nerves supplying the pharyngeal arches. B , Sketch of the head and neck regions of a 20-week fetus shows the superficial distribution of the two caudal branches of the first arch nerve (cranial nerve V). C , Sagittal section of the fetal head and neck shows the deep distribution of sensory fibers of the nerves to the teeth and mucosa of the tongue, pharynx, nasal cavity, palate, and larynx.

The facial skin is supplied by the trigeminal nerve (CN V); however, only its caudal two branches (maxillary and mandibular) supply derivatives of the first arch (see Fig. 9.6 B ). CN V is the principal sensory nerve of the head and neck and is the motor nerve for the muscles of mastication (see Table 9.1 ). Its sensory branches innervate the face, teeth, and mucous membranes of nasal cavities, palate, mouth, and tongue (see Fig. 9.6 C ).

The facial nerve (CN VII), glossopharyngeal nerve (CN IX), and vagus nerve (CN X) supply the second, third, and fourth to sixth (caudal) arches, respectively. The fourth arch is supplied by the superior laryngeal branch of CN X and by its recurrent laryngeal branch. The nerves of the second to sixth arches have little cutaneous distribution (see Fig. 9.6 C ), but they innervate the mucous membranes of the tongue, pharynx, and larynx.

Pharyngeal Pouches

The primordial pharynx , which is derived from the foregut, widens cranially as it joins the stomodeum (see Figs. 9.3 A and B and 9.4 B ) and narrows as it joins the esophagus. The endoderm of the pharynx lines the internal aspects of the arches and the pharyngeal pouches (see Figs. 9.1 H to J and 9.3 B and C ). The pouches develop as outpocketing of the endoderm in a craniocaudal sequence between the arches. The first pair of pouches, for example, lies between the first and second arches. Four pairs of pouches are well defined; the fifth pair (if present) is rudimentary. The endoderm of the pouches contacts the ectoderm of the pharyngeal grooves, and they form the double-layered pharyngeal membranes that separate the pouches from the grooves (see Figs. 9.1 H and 9.3 C ). Retinoic acid, Wnt, and fibroblast growth factor (Fgf) signaling play an essential role in the formation and differentiation of the pharyngeal pouches.

Derivatives of Pharyngeal Pouches

The endodermal epithelial lining of the pouches forms important organs in the head and neck.

First Pharyngeal Pouch

The first pouch expands into an elongated tubotympanic recess ( Fig. 9.7 B ). The expanded distal part of this recess contacts the first groove, where it later contributes to the formation of the tympanic membrane (eardrum). The cavity of the tubotympanic recess becomes the tympanic cavity and mastoid antrum . The connection of the tubotympanic recess with the pharynx gradually elongates to form the pharyngotympanic tube (auditory tube).

Fig. 9.7, Schematic horizontal sections at the level shown in Fig. 9.5 A illustrate the adult derivatives of the pharyngeal pouches. A , At 5 weeks, the second arch grows over the third and fourth arches, burying the second to fourth grooves in the cervical sinus. B , Development at 6 weeks. C , At 7 weeks, the developing thymus, parathyroid, and thyroid glands migrate into the neck (arrows) .

Second Pharyngeal Pouch

Although the second pouch is largely obliterated as the palatine tonsil develops, part of the cavity of this pouch remains as the tonsillar sinus (fossa), the depression between the palatoglossal and palatopharyngeal arches ( Fig. 9.8 ; see Fig. 9.7 C ). The endoderm of the second pouch proliferates and grows into the underlying mesenchyme. The central parts of these buds break down, forming tonsillar crypts (pit-like depressions). The pouch endoderm forms the surface epithelium and lining of the tonsillar crypts. At approximately 20 weeks, the mesenchyme around the crypts differentiates into lymphoid tissue , which soon organizes into the lymphatic nodules of the palatine tonsil (see Fig. 9.7 C ). Initial lymphoid cell infiltration occurs at approximately the seventh month, with germinal centers forming in the neonatal period and active germinal centers within the first year of life.

Fig. 9.8, Schematic sagittal section of the head, neck, and upper thoracic regions of a 20-week fetus shows the adult derivatives of the pharyngeal pouches and the descent of the thyroid gland into the neck (broken line) .

Third Pharyngeal Pouch

The third pouch expands and forms a solid, dorsal, bulbar part and a hollow, elongated, ventral part (see Fig. 9.7 B ). Its connection with the pharynx is reduced to a narrow duct that soon degenerates. By the sixth week, the epithelium of each dorsal bulbar part of the pouch begins to differentiate into an inferior parathyroid gland . The epithelium of the elongated ventral parts of the pouch proliferates, obliterating their cavities. These parts come together in the median plane to form the thymus , which is a primary lymphoid organ (see Fig. 9.7 C ). The bilobed structure of this lymphatic organ remains throughout life, discretely encapsulated.

Each lobe has its own blood supply, lymphatic drainage, and nerve supply. The developing thymus and inferior parathyroid glands lose their connections with the pharynx when the brain and associated structures expand rostrally, and the pharynx and cardiac structures expand caudally. The derivatives of pouches two to four become displaced caudally. Later, the parathyroid glands separate from the thymus and lie on the dorsal surface of the thyroid gland (see Figs. 9.7 C and 9.8 ). The fibroblast growth factor–signaling pathways, acting through fibroblast growth factor–receptor substrate 2 (FRS2), are involved in the development of the thymus and parathyroid glands.

Histogenesis of Thymus

The thymus is a primary lymphoid organ that develops from epithelial cells derived from endoderm of the third pair of pouches and from mesenchyme into which epithelial tubes grow. The tubes soon become solid cords that proliferate and form side branches. Each side branch becomes the core of a lobule of the thymus. Some cells of the epithelial cords become arranged around a central point, forming small groups of cells called thymic corpuscles (Hassall corpuscles). Other cells of the epithelial cords spread apart, but they retain connections with each other to form an epithelial reticulum. The mesenchyme between the epithelial cords forms thin, incomplete septa between the lobules.

Lymphocytes soon appear and fill the interstices between the epithelial cells. The lymphocytes are derived from hematopoietic stem cells . The thymic primordium is surrounded by a thin layer of mesenchyme that is essential for its development. Neural crest cells also contribute to thymic organogenesis.

Growth and development of the thymus are not complete at birth. It is a relatively large organ during the perinatal period and may extend through the superior thoracic aperture at the root of the neck. As puberty is reached, the thymus begins to diminish in relative size as it undergoes involution. By adulthood, it is often scarcely recognizable because of fat infiltrating the cortex of the gland; however, it is still functional and important for the maintenance of health. In addition to secreting thymic hormones, the thymus primes thymocytes (T-cell precursors) before releasing them to the periphery.

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