1. Embryology of the Head & Neck

Germ Layers & the Developing Embryo

Fig. 1.1 Embryonic development (after Sadler)

Age in postovulatory days.

A-C Posterior (dorsal) view after removal of the amnion.

D-E Schematic cross-sections of the corresponding stages at the horizontal planes of section marked in A to C. Gastrulation occurs in week 3 of human embryonic development. It produces three germ layers in the discus embryonicus: ectoderma (light grey), mesoderma (red), and endoderma (dark grey).

A, D Day 19, the three layers are visible in the discus embryonicus. The amnion forms the cavitas amniotica dorsally and the endoderma encloses the saccus vitellinus. The tubus neuralis is developing in the area of the lamina neuralis.

B, E Day 20, the first somiti have formed, and the sulcus neuralis is beginning to close to form the tubus neuralis, with initial folding of the embryo.

C, F Day 22, eight pairs of somiti flank the partially closed tubus neuralis, which has sunk below the ectoderma. The saccus vitellinus elongates ventrally to form the gut tube and saccus vitellinus. At the sites where the plicae neurales fuse to close the tubus neuralis, cells form a bilateral crista neuralis that detaches from the surface and migrates into the mesoderma.

Fig. 1.2 Somatic muscle development

Age in postovulatory days. Each somitus divides into a dermatome (cutaneous), myotome (muscular), and sclerotome (vertebral) at around day 22 (see Fig 1.1).

A Day 28, sclerotomes migrate to form the columna vertebralis around the notochorda (primitive medulla spinalis).

B Day 30, all 34 or 35 somitus pairs have formed. The tubus neuralis differentiates into a primitive medulla spinalis. Motor and sensory neurons differentiate in the cornua anterius and posterius of the medulla spinalis, respectively.

C By day 40, the radices posterior and anterior form the mixed nervus spinalis. The ramus posterior supplies the epiaxial muscles (future musculi dorsi proprii); the ramus anterior supplies the hypaxial muscles (anterior muscles, including all muscles except the musculi dorsi proprii).

D Week 8, the epiaxial and hypaxial muscles have differentiated into the skeletal muscles of the trunk. Cells from the sclerotomes also migrate into the limbs. During this migration, the nervi spinales form the plexus (cervicalis, brachialis, and lumbosacralis), which innervate the muscles of the neck, upper limb, and lower limb, respectively.

Fig. 1.3 5-week-old embryo

The human embryo at 5 weeks has a crown-rump length of approximately 5 to 7 mm. The funiculus umbilicus, which attaches the embryo to the mother, is seen. The future hemispheria cerebri form along with the oculus, auris, arcus pharyngei (which form a large portion of the structures of the caput and collum), cor (which will start beating at around week 6), tubus neuralis, and gemmae membrorum.

Development of the Encephalon & Medulla Spinalis

Fig. 1.4 Development of the tubus neuralis and crista neuralis (after Wolpert)

The tissues of the nervous system orginate embryonically from the posterior surface ectoderma. The notochorda in the midline of the body induces the formation of the lamina neuralis, which lies above the notochorda, and of the cristae neurales, which are lateral to the notochorda. With further development, the lamina neuralis deepens at the center to form the sulcus neuralis, which is flanked on each side by the plicae neurales. Later the sulcus deepens and closes to form the tubus neuralis, which sinks below the ectoderma. The tubus neuralis is the structure from which the systema nervosum centrale (CNS) − the brain and medulla spinalis−develops (further development of the medulla spinalis is shown in Fig. 1.5, further encephalon development in Fig. 1.7). Failure of the sulcus neuralis to close completely will leave an anomalous cleft in the columna vertebralis, known as spina bifida. The administration of folic acid to potential mothers around the time of conception can reduce the incidence of spina bifida by 70%. Cells that migrate from the crista neuralis develop into various structures, including cells of the systema nervosum periphericum (PNS), such as Schwann cells, and the pseudounipolar cells of the ganglion sensorium nervi spinalis (see Fig. 1.6).

Fig. 1.5 Differentiation of the tubus neuralis in the medulla spinalis during development

Cross-section, superior view.

A Early tubus neuralis. B Intermediate stage. C Adult medulla spinalis. The neurons that form the lamina ventrolateralis are efferent (motor neurons), while the neurons that form the lamina dorsolateralis are afferent (sensory neurons). In the future thoracic, lumbar, and sacral medulla spinalis, there is another zone between them that gives rise to sympathetic (autonomic) efferent neurons. The lamina dorsalis and the lamina ventralis do not form neurons.

Fig. 1.6 Development of a peripheral nerve

Afferent (sensory) axons (blue) and efferent (motor) axons (red) sprout from the neuronal cell bodies during early embryonic development.

A Primary afferent neurons develop in the ganglion sensorium nervi spinalis, and alpha motor neurons develop from the lamina ventrolateralis of the medulla spinalis.

B The interneurons (black), which functionally interconnect the afferent and efferent neurons, develop at a later stage.

Fig. 1.7 Development of the encephalon

A Embryo with the greatest length (GL) of 10 mm at the beginning of the 2nd month of development. Even at this stage, we can see the differentiation of the tubus neuralis into segments that will generate various brain regions.

• Red: telencephalon (cerebrum)

• Yellow: diencephalon

• Dark blue: mesencephalon (midbrain)

• Light blue: cerebellum

• Gray: pons and medulla oblongata

Note: The telencephalon outgrows all of the other brain structures as development proceeds.

B Embryo with a GL of 27 mm near the end of the 2nd month of development (end of the embryonic period). The telencephalon and the diencephalon have enlarged. The bulbus olfactorius is developing from the telencephalon, and the primordium of the hypophysis is developing from the diencephalon.

C Fetus with a GL of 53 mm in approximately the 3rd month of development. By this stage the telencephalon has begun to cover the other brain areas. The insula is still on the brain surface but will subsequently be covered by the hemispheria (compare with D).

D Fetus with GL of 27 cm (270 mm) in approximately the 7th month of development. The cerebrum (telencephalon) has begun to develop well-defined gyri and sulci.

Development & Derivatives of the Arcus Pharyngei

Fig. 1.8 Head and neck region of a 5-week-old embryo, showing the arcus and sulci pharyngei

Left lateral view. The arcus pharyngei are instrumental in the development of the face, neck, larynx, and pharynx. Development of the arcus pharyngei begins in the 4th week of embryonic life as cells migrate from the crista neuralis to the future head and neck region. Within 1 week, a series of four cristae obliquae (first through fourth arcus pharyngei) form that are located at the level of the cranial segment of the foregut and are separated externally by four deep sulci (sulci pharyngei). The arcus and sulci pharyngei are prominent features of the embryo at this stage.

Fig. 1.9 Cross-section through an embryo at the level of the pharyngeal gut (after Drews)

Left superior oblique view. Due to the craniocaudal curvature of the embryo, the cross-section passes through the arcus pharyngei and pharyngeal gut as well as the prosencephalon and medulla spinalis. The pharyngeal gut is bounded on both sides by the arcus pharyngei, which contain the mesodermal core. They are covered externally by ectoderm and internally by endoderm. Ectodermal sulci pharyngei and endodermal sacci pharyngei lie directly opposite one another. Because the embryo is curved craniocaudally, the pharyngeal gut and arcus pharyngei overlie the prominence of the rudimentary heart and liver.

Fig. 1.10 Structure of the arcus pharyngei (after Sadler)

A Cross-section through an arcus pharyngeus and the tubus neuralis, showing the cartilago and arteria arcus pharyngei. B Oblique cross-section through an arcus pharyngeus and the tubus neuralis, showing the nervi arcus pharyngei. C Blow up of section in B, showing the relationship of cartilago, arteria, and nervus in the arcus pharyngei.

The arcus pharyngei are covered externally by ectoderma (blue) and internally by endoderma (green). Each arcus pharyngeus contains an arteria arcus, an nervus arcus, and a cartilaginous skeletal element, all of which are surrounded by mesenchyma and muscular tissue. The external grooves are called the sulci pharyngei, and the internal grooves are called the sacci pharyngei.

Fig. 1.11 The arrangement and derivatives of the arcus pharyngei (after Sadler and Drews)

A The arcus pharyngei with the associated nervi arcuum pharyngeorum

B The nervus mandibularis (CN V₃), nervus facialis (CN VII), nervus glossopharyngeus (CN IX), and nervus vagus (CN X) derived from the nervi arcuum pharyngeorum

C Muscles derived from the arcus pharyngei

D Skeletal and ligamentous elements derived from the arcus pharyngei

Development & Derivatives of the Sacci Pharyngei, Membranae Pharyngeae, & Sulci Pharyngei

Fig. 1.12 Development of the sacci pharyngei, membranae pharyngeae, and sulci pharyngei

A Schematic view of developing sacci and sulci pharyngei.

B Schematic view of adult structures formed by sacci pharyngei.

C Three-dimensional representation of the sacci pharyngei and their relationship to the cavitas oris, cavitas pharyngis, and structures of the neck.

The sacci pharyngei are paired, diverticula-like outpouchings of the endodermal pharyngeal gut. A total of four distinct sacci pharyngei develop on each side; the fifth is often absent or rudimentary. The sacci pharyngei develop into the cavitas tympani and the glandulae endocrinae in the neck.

The sulcus pharyngeus primus develops into the emeatus acusticus externus. The arcus pharyngeus secundus grows over the arcus pharyngei tertius and quartus and as it does so it buries the sulci pharyngei secundus, tertius, and quartus pharyngeal clefts. Remnants of these clefts form the sinus cervicalis, which is normally obliterated.

The membranae pharyngeae separate the sacci pharyngei from the sulci pharyngei in the developing embryo. They collectively develop into the membrana tympanica.

Fig. 1.13 Pharyngeal pouches and the aortic arch (after Sadler)

The arteriae arcuum pharyngeorum arise from the paired embryonic aortae ventrales and run between the sacci pharyngei. They open posteriorly into the aortae dorsales, which is also paired. The definitive arcus aortae develops arteria quarti arcus pharyngei sinistri.

Note: The pouch protruding from the roof of the cavitas oris is called Rathke’s pouch (precursor of the adenohypophysis). Note also the gemma pulmonalis extending anteriorly from the pharyngeal gut, and the primordium glandulae thyroideae.

Table 1.5 Derviative of the membranae pharyngeae

Membranes	Germ layers	Adult structure
1 to 4	Composed externally of ectoderma and internally of endoderma. The intervening core consists of mesoderma and crista neuralis cells.	Membrana tympanica

Table 1.6 Derivatives of the pharyngeal clefts

Cleft	Germ layer	Adult structure
1	Ectoderma	Meatus acusticus externa
2 to 4		Sinus cervicalis, which is rapidly obliterated by the arcus pharyngeus secundus, which grows over sulci II to IV

Treacher Collins syndrome is a rare autosomal dominant craniofacial defect involving the structures derived from the arcus pharyngeus primus. It is characterized by malar hypoplasia (underdevelopment or incomplete development of the cheek), mandibular hypoplasia, downslanting eyes, eyelid coloboma (notching of the lower eyelids), and malformed aures externae. It may also be associated with cleft palate, hearing loss (due to defects in the ossicles), vision loss, and difficulty breathing (dyspnea). Treatment will depend on the severity of the defects but will involve a multidisciplinary team of clinicians.

Pierre-Robin syndrome is characterized by an abnormally small mandibula (micrognathia). As a result, the tongue musculature is unsupported by the mandibula, allowing it to displace posteriorly, partially obstructing the airway, resulting in dyspnea (shortness of breath). This posterior displacement of the tongue (glossoptosis) is also responsible for cleft palate because it prevents the processus palatini laterales from fusing (see Figs. 1.21 and 1.22). Initial treatment involves surgery to repair the cleft palate to improve feeding and speech development.

Development of the Lingua & Glandula Thyroidea

Fig. 1.14 Development of the lingua

A Early tongue development, around week 4. B Late tongue development, around week 8.

The lingua develops within the pharynx. While the musculature of the lingua is derived from somiti, the lingua develops from the four gemmae linguales. Three gemmae are associated with the arcus pharyngeus primus and one, with the arcus tertius, quartus, and sextus. The two gemmae linguales laterales and one gemma lingualis mediana (the tuberculum impar) from the arcus pharyngeus primus contribute to the development of the anterior two thirds of the lingua. The single midline swelling (the eminentia hypopharyngea [copula]) from the arcus tertius, quartus, and sextus contributes to the development of the posterior one third of the lingua. A U-shaped sulcus develops around the lingua allowing it to move freely, except in one area, which is the frenulum linguae, which anchors the lingua to the floor of the cavitas oris.

The lingual mucosa derived from the arcus primus swelling that covers the anterior two thirds of the tongue is innervated by the nervus mandibularis division of the nervus trigeminus; the lingual mucosa derived from the arcus tertius, quartus, and quintus swellings receives sensory innervation from both CN IX (nervus hypoglossus) and CN X (nervus vagus).

The V-shaped (sulcus terminalis) separates the anterior two thirds of the lingua from the posterior one third. Located at the vertex of the sulcus terminalis, between the tuberculum impar and the eminentia hypopharyngea, the foramen caecum marks the site of exit for the glandula thyroidea from the floor of the inside of the pharynx to an extrapharyngeal location.

Ankyloglossia (tongue-tie) is a congenital anomaly in which the frenulum linguae is unusually short or thick, thereby tethering the ventral surface of the tip of the lingua to the floor of the mouth. Clinical features include restricted elevation, protrusion, and side-to-side movement of the lingua, and demonstration of a heart-shaped lingua on protrusion. It may be noticed as difficulty feeding in infants. Treatment, when required, involves a frenectomy, where the frenulum is incised, releasing the lingua.

Table 1.8 Derivation of the skeletal muscles of the lingua

Muscle origin	Muscles	Nervi craniales
Somiti (from myotomes)	Intrinsic muscles of the lingua Extrinsic muscles of the lingua (musculi genioglossus, styloglossus, and hyoglossus; not musculus palatoglossus)	Nervus hypoglossus (CN XII)

Fig. 1.15 Migration of the arcus pharyngeus tissues (after Sadler)

Anterior view. During embryonic development, the epithelium from which the glandula thyroidea forms migrates from its site of origin on the basal midline of the lingua to the level of the first tracheal cartilage, where the glandula thyroidea is located in postnatal life. As the thyroid tissue buds off from the lingua base, it leaves a vestigial depression on the dorsum linguae, the foramen caecum. The glandulae parathyroideae are derived from the arcus pharyngeus quartus (superior pair) or the arcus pharyngeus tertius (inferior pair), which also gives rise to the thymus. The ultimobranchial body, whose cells migrate into the glandula thyroidea to form the calcitonin-producing C cells, or parafollicular cells, is derived from the 5th vestigial arcus pharyngeus. The latter arch is the last to develop and is usually considered part of the arcus pharyngeus quartus. The meatus acusticus externus is derived from the sulcus pharyngeus primus, the cavitas tympani and tuba auditiva from the saccus pharyngeus primus, and the tonsilla palatina from the saccus pharyngeus secundus.

Ectopic thyroid is a rare condition in which the entire glandula thyroidea or thyroid tissues are not found in their normal position in the neck, i.e., inferolateral to the cartilago thyroidea. Dentists may encounter this as a firm midline mass, which may appear as light pink to bright red, and may be regular or irregular on the dorsum linguae, just posterior to the foramen caecum (the embryonic origin of the glandula thyroidea). This is known as a lingual thyroid and represents approximately 90% of ectopic thyroid cases. Symptoms of lingual thyroid may include cough, pain, difficulty swallowing (dysphagia), difficulty speaking (dysphonia), and difficulty breathing (dyspnea).

Fig. 1.16 Location of cysts and fistulas in the neck

A Median cysts. B Median fistulas. C Lateral fistulas and cysts.

A, B Median cysts and fistulas in the neck are remnants of the ductus thyroglossus. Failure of this duct to regress completely may lead to the formation of a mucus-filled cavity (cyst), which presents clinically as a palpable, fluctuant, midline swelling in the neck at around the level of the os hyoideum. It is seen to move upward on swallowing or protrusion of the lingua due to the connection of the lingua with the duct. Symptoms may include dyspnea (difficulty breathing), dysphagia (difficulty swallowing), and pain (only if the cyst becomes infected).

C Lateral cysts and fistulas in the neck are anomalous remnants of the ductal portions of the sinus cervicalis, which forms as a result of tissue migrations during embryonic development.

If epithelium-lined remnants persist, neck cysts (right) or fistulas (an abnormal communication between structures; left) may appear in postnatal life. A complete fistula opens into the pharynx and onto the surface of the skin, whereas an incomplete (blind) fistula is open at one end only. The external orifice of a lateral cervical fistula is typically located at the anterior border of the musculus sternocleidomastoideus.

Development of the Face

Fig. 1.17 Development of the face (after Sadler)

A Anterior view at 24 days. The surface ectoderma of the arcus pharyngeus primus invaginates to form the stromodeum, which is a depression between the prosencephalon and the pericardium in the embryo. It is the precursor of the mouth, cavitas oris, and the adenohypophysis. At this stage, the stromodeum is separated from the primitive pharynx by the buccopharyngeal (oropharyngeal) membrane. This membrane later breaks down and the stromodeum becomes continuous with the pharynx.

The stromodeum is surrounded by five neural-crest-cell−derived mesenchymal swellings, known as prominentiae, which contribute to the development of the face.

B Anterior view at 5 weeks. Placodae nasales, ectodermal thickenings, form on each side of the prominentia frontonasalis. Invagination of the placodae nasales into the prominentia frontonasalis leads to the formation of the prominentiae nasales lateralis and medial is. The placodae now lie in the floor of a depression known as the fovea nasalis. The prominentiae maxillares continue to increase in size and merge laterally with the prominentiae mandibulares to form the cheek. Medially, the prominentiae maxillares compress the prominentiae nasales mediales toward the midline. A furrow (the sulcus nasolacrimalis) separates the prominentiae nasales from the prominentia maxillaris. Ectoderma from the floor of the sulcus nasolacrimalis will give rise to the ductus nasolacrimalis that connects the orbita with the cavitas nasi; the two prominences will join to close the groove and create the canalis nasolacrimalis.

C Anterior view at 6 weeks. The prominentiae nasales mediales enlarge, grow medially, and merge with each other to form the intermaxillary segment.

D Anterior view at 7 weeks. The prominentiae nasales mediales have fused with each other along the midline and with the prominentiae maxillares and their lateral margins.

E Anterior view at 10 weeks. Cell migration is complete.

Table 1.9 Prominences contributing to facial structures

Prominence	Facial structure
Prominentia frontonasalis	Forehead, nose, prominentiae nasales medialis and lateralis
Prominentiae maxillares	Cheeks, lateral parts of the labium superius
Prominentiae nasales mediales	Philtrum of the labium superius, dorsum and apex nasi
Prominentiae nasales laterales	Alae nasi
Prominentiae mandibulares	Labium inferius
*The prominentia frontonasalis is a single unpaired structure; all other prominences listed as paired.

Fig. 1.18 Development of the cavitas nasi

Sagittal section of embryo. At week 6, the primitive cavitas nasi is separated from the cavitas oris by the membrana oronasalis (A), which then breaks down (B), leaving the cavitates nasi and oris in open connection by week 7 (C). In week 9, the cavitas nasi and cavitas oris are in their definitive arrangement (D), separated by the palata primarium and secundarium with choanae at their junction in the pharynx. The lateral walls of the cavitas nasi develop the conchae superior, media, and inferior. The ectodermal epithelium in the roof of the cavitas nasi becomes the specialized olfactory epithelium. The olfactory cells within the olfactory epithelium give rise to the fila olfactoria (CN I) that grow into the bulbus olfactorius. The septum nasi (not shown) develops as a downgrowth of the merged prominentiae nasales mediales. It fuses with the processus palatinus by weeks 9 to 12.

Fig. 1.19 Development of the oculi and aures

At about 22 days, the oculi and aures begin to develop. The oculi develop laterally in the embryo but during growth move medially to occupy their familiar position on the face. The auricula of the auris is formed from six swellings, known as colliculi auriculares, from the sacci pharyngei primus and secundus. The germ layers that contribute to the oculi and aures are listed in Table 1.10.

Table 1.10 Derivation of the structures of the oculus and auris

Germ layer	Structure
Oculus
Surface ectoderma	Corneal and conjunctival epithelium, lens, glandulae lacrimales, glandulae tarsales
Crista neuralis cell ectoderma (neuroectoderm)	Retina, nervus opticus (CN I), iris
Mesenchyma	Corneal stroma, sclera, choroidea, iris, parts of corpus vitreum, musculus ciliaris, muscles lining the camera anterior
Auris
Ectoderma	Meatus acusticus externus
Endoderma	Auricula
Mesenchyma	Organum vestibulocochleare

Development of the Palatum

Fig. 1.20 Palatum formation, 7- to 8-week-old embryo

Inferior view. Before the palatum has formed, the cavitas oris is open to the cavitas nasi. The septum nasi can be seen as well as the membrana oronasalis, which will ultimately form the choana. Development of the palatum begins during week 5, but fusion of its parts is not complete until week 12. The most critical period for palatum development is between the end of week 6 and the beginning of week 9. The palatum forms from two major parts, the palata primarium and secundarium. The palatum primarium is derived from the wedge-shaped intermaxillary segment, which is formed by the merging of the two prominentiae nasales mediales. The palatum secundarium is derived from two shelflike outgrowths of the prominentia maxillaris, which, at this stage, are directed downward beside the lingua (removed).

Fig. 1.21 Elevation of the processus palatini laterales

The processus palatini laterales, which form the palatum secundarium, are seen at around 6 weeks and are directed obliquely downward on each side of the lingua. At around 7 weeks, the processus palatini laterales ascend to a horizontal position above the lingua and fuse.

Fig. 1.22 Fusion and merging of the processus palatini laterales

Fusion of the palatum begins at around 9 weeks and is completed posteriorly by week 12. (A) The palatum primarium and both halves of the palatum secundarium migrate toward each other as indicated by the arrows. (B) They contact and fuse at a point (marked by the foramen incisivum) and merge anteriorly and posteriorly, as shown in (C) and (D). The palata primarium and secundarium ossify, forming the palatum durume. The posterior portions of the processus palatini laterales do not become ossified but extend beyond the septum nasi to form the palatum molle and uvula.

Fig. 1.23 Formation of facial clefts (after Sadler)

Inferior view.

Clefts (fissures or openings) can involve the labium and/or the palatum. Clefts are classified as isolated (cleft lip or cleft palate), unilateral or bilateral, and as complete (when they cross the nasal philtrum) or incomplete (if they do not cross the nasal philtrum).

A Normal labium and palatum, in which the prominentiae maxillares and prominentiae nasales mediales have merged to form the labium superius and palatum primarium. The palatum primarium has also fused with the processus palatini of the prominentiae maxillares (palata primarium) to form the complete, unified, palatum durum. The posterior portion of the palatum secundarium is unossified and forms the palatum molle and uvula.

B Unilateral, complete cleft labium results from failure of fusion of the maxillary prominence with the prominentia nasalis medialis on the affected side.

C Unilateral, complete cleft lip, alveolus, and palatum primarium (part of palatum anterior to the foramen incisivum) results from failure of fusion of the prominentia maxillaris with the prominentia nasalis medialis on the affected side.

D Bilateral, complete cleft labium, alveolus, and palatum primarium result from failure of the prominentiae maxillares to fuse with the prominentiae nasales mediales on both sides.

E Cleft of palatum secundarium (part of palatum posterior to the foramen incisivum) results from incomplete fusion of the two processus palatini laterales.

F Unilateral, complete cleft labium and complete cleft palatum (involving both palata primarium and secundarium) result from failure of fusion of the prominentia maxillaris with the prominentia nasalis medialis and failure of fusion of the two processus palatini laterales on the affected side.

Cleft labium and palatum can cause difficulty in eating and speaking, and result in failure to thrive in infants. Treatment by a multidisciplinary team of healthcare professionals principally involves corrective surgery, which is usually performed between 6 and 12 months of age, often followed by surgical revisions, speech therapy, and orthodontic therapy.