Development of the head and neck

Skeletal elements of the pharyngeal arches

In human embryos, neural crest mesenchyme in the first three arches gives rise to ligaments, tendons, connective tissue and cartilage that forms skeletal elements that subsequently chondrify in part or in their entirety. Where chondrogenesis is complete, the element contacts the skull base lateral to the hindbrain ( Figs 17.5 – 17.6 ). No cartilages form in the fourth and sixth arches in human embryos ( ).

The first arch cartilage, Meckel’s cartilage, is a structure around which the embryonic lower jaw skeleton arises. After the mandible forms by intramembranous ossification of the neural crest mesenchyme lateral to it, Meckel’s cartilage degenerates but its sheath persists as the anterior malleolar and sphenomandibular ligaments. At its proximal end, endochondral ossification forms two of the middle ear bones, the malleus and incus. These are homologous with the articular and quadrate bones that form the reptilian jaw articulation, where the quadrate forms from the caudal end of the palatopterygoquadrate cartilage. The mammalian evolutionary derivatives of this cartilage are thought to include part of the greater wing of the sphenoid bone, the roots of its pterygoid plates and the incus.

The second arch cartilage, Reichert’s cartilage, forms from neural crest mesenchyme that extends from the proximity of the otic capsule dorsally toward the median plane ventrally. It gives rise to the stapes, which is the most ancient of the three auditory ossicles, homologous with the rod-shaped columella auris of reptiles and birds, and the styloid process proximally and the lesser cornua of the hyoid bone distally: the stylohyoid ligament develops between these two bones (see Fig. 17.6 ). Cartilage in the third arch, also derived from neural crest mesenchyme, gives rise to the greater cornua of the hyoid bone. The body of the hyoid bone develops from a ventral mesenchymal population without contributions from the distal second and third arch cartilages. The laryngeal cartilages associated with arches 4 and 6 (thyroid, cricoid and arytenoid) arise from mesenchymal condensations in the ventral neck: fourth and sixth arch cartilages are not seen in human embryos ( ).

Muscles of the pharyngeal arches

The striated muscle of each arch is derived from cranial paraxial mesoderm, which is unsegmented rostral to the occipital region, whereas more caudally segmentation gives rise to four pairs of epithelial somites that are similar to those of the trunk, except that the first pair is rather poorly defined. Myoblasts migrate from the paraxial mesoderm to sites of future muscle differentiation and form pre-muscle condensations prior to the development of any skeletal elements. The pattern of primary myotube alignment for any one muscle is specified by the surrounding neural crest-derived mesenchyme. The rate and pattern of muscle maturation are closely associated with the development of the skeletal elements. Fig. 17.7 illustrates the muscle masses of each arch, their innervation and their derivatives in the adult.

The muscle mass of the mandibular part of the first arch forms tensor tympani, tensor veli palatini, mylohyoid, anterior belly of digastric and the masticatory muscles. Tensor tympani retains its connection with the skeletal element of the arch through its attachments to the malleus, and tensor veli palatini remains attached to the base of the medial pterygoid process, which may itself be derived from the dorsal cartilage of the first arch. All of these muscles are supplied by the mandibular nerve, the mixed nerve of the first arch. The maxillary division of the trigeminal nerve has no motor component, because no muscles are derived from maxillary mesenchyme.

The muscles of the second arch migrate widely but retain their original nerve supply from the facial nerve. Their migration is facilitated by the early obliteration of part of the first pharyngeal cleft and pouch. Stapedius, stylohyoid and posterior belly of digastric remain attached to the hyoid bone but the facial musculature, platysma, auricular muscles and occipitofrontalis all lose their connection with it.

The muscle masses from the third and fourth arches form the musculature of the pharynx, larynx and soft palate. Stylopharyngeus is a third arch muscle, and is innervated by a branch of the glossopharyngeal nerve. All of the intrinsic laryngeal muscles are innervated by the vagus nerve: the cricothyroid by the superior laryngeal branch to the fourth arch and the others by the recurrent laryngeal nerve, which has been considered to be the sixth arch nerve. Precise arch origins are not clearly defined for the palatal muscles (except tensor veli palatini), or for the pharyngeal constrictors; these muscles all receive their nerve supply via the pharyngeal plexus (see Ch. 40 ). The extraocular muscles are not associated with the pharyngeal arches but are derived from mesenchyme arising from the prochordal plate that migrates to differentiate adjacent to the eyes ( Ch. 15 ).

Nerves of the pharyngeal arches

The cranial nerves associated with each arch arise from the adjacent hindbrain (see Fig. 17.7 ; see also Figs 12.4 , 14.19 ). They are the trigeminal (V), facial (VII), glossopharyngeal (IX), vagus (X) and cranial and spinal accessory (XI) nerves. The motor nerves extend from the basal plate of the hindbrain to innervate the striated muscle of the arches and are termed special visceral efferent nerves because they innervate pharyngeal musculature. Sensory nerves extend peripherally and centrally from cranial ganglia that are formed partly from neural crest and partly from cells that delaminate from epibranchial placodes; they convey general and special somatic afferent axons. Each arch is innervated by a mixed nerve, but the nerves of the first three arches also have a purely sensory branch that innervates the arch rostral to its ‘own’ arch; this sensory nerve is called the pretrematic branch because it extends rostral to the cleft (trema) between the two arches (see Figs 17.3 , 17.7 ). The nerves to the mandibular arch include the mandibular division of the trigeminal nerve, which is mixed, and the chorda tympani, the purely sensory pretrematic branch of the facial nerve. The maxillary branch of the trigeminal and the tympanic branch of the glossopharyngeal are also considered to be pretrematic nerves. The ophthalmic branch of the trigeminal nerve, which supplies the frontonasal area, is not an arch nerve; in fishes, its ganglion is separate from the first arch nerve ganglion.

The vagus nerve supplies the fourth and sixth arches (see Fig. 17.7 ). The recurrent laryngeal branch initially loops under the sixth arch artery on both sides, but the asymmetric changes to the vascular system affect the symmetry of this nerve. On the right, when the sixth aortic arch lateral to the right pulmonary artery degenerates, the recurrent laryngeal nerve usually loops under the fourth arch-derived subclavian artery; on the left, it loops round the ductus arteriosus (which is retained as the ligamentum arteriosum in the adult). Further details of cranial nerve development and composition are provided in Chapter 14 .

Blood vessels of the pharyngeal arches

Pharyngeal arch arteries

The heart outflow tract initially develops by vasculogenesis soon after neural crest cells have invaded the early pharyngeal arches. Angiogenic mesenchyme migrates into the neural crest-populated areas and forms the endothelial lining of the vessels, and neural crest contributes to the outer layers of the walls ( , ). The first aortic arch artery is part of the original vascular circuit that links the aortic sac of the heart to the paired dorsal aortae, blood returning to the heart via the allantoic, vitelline and common cardinal veins (see Fig. 13.1C ). As the heart descends relative to the forebrain and other rostral structures, the aortic sac (ventral aortic root) gives rise to paired aortic arches at successively more caudal levels, each of which passes laterally on each side of the pharynx to join the dorsal aortae. The dorsal aortae are not invested by neural crest cells, and nor are the more distal (cranial) parts of the carotid arteries, which form by angiogenesis ( Ch. 13 ). The whole complement of aortic arches never coexists, thus the first aortic arch degenerates through remodelling of the cranial arteries before the sixth is formed.

When the first and second aortic arch arteries begin to regress, the blood supply to the corresponding pharyngeal arches is derived from a transient ventral pharyngeal artery, which terminates by dividing into mandibular and maxillary branches. The second aortic arch artery at first anastomoses with the ventral pharyngeal artery and passes through the mesenchyme of the stapedial cartilage, which condenses around it, forming the foramen of the stapes.

Further development of the third, fourth and sixth aortic arches ( Figs 17.8 – 17.9 ) produces the main arteries to the head and the great vessels arising from the heart. The common carotid artery arises from an elongation of the aortic sac, and the third arch artery becomes the proximal part of the internal carotid artery. The external carotid artery arises as a sprout from the common carotid; it incorporates the stem of the ventral pharyngeal artery, and its maxillary branch communicates with the common trunk of origin of the maxillary and mandibular branches of the stapedial artery and annexes these vessels. The proximal part of the common trunk persists as the root of the middle meningeal artery (see Fig. 17.8 ). More distally, the meningeal artery is derived from the proximal part of the supraorbital artery. The maxillary branch becomes the infraorbital artery and the mandibular branch forms the inferior alveolar artery. When the definitive ophthalmic artery differentiates as a branch from the terminal part of the internal carotid artery, it communicates with the supraorbital branch of the stapedial artery, which becomes the lacrimal artery distally, and retains an anastomotic connection with the middle meningeal artery. The dorsal stem of the original second arch artery remains as one or more caroticotympanic branches of the internal carotid artery.

The fourth aortic arch on the right forms the proximal part of the right subclavian artery, whereas the corresponding vessel on the left constitutes the arch of the definitive aorta between the origins of the left common carotid and left subclavian arteries. With elongation of the neck, longitudinal anastomoses in the cervical region link intersegmental arteries and their branches, and direct blood flow to the developing brain in the vertebral arteries in parallel with the internal carotid arteries (see Figs 17.8 – 17.9 ).

The sixth aortic arch is associated with the developing lung buds. Initially, each bud is supplied by a capillary plexus from the aortic sac. As the sixth aortic arch develops, it becomes the channel for blood from the aortic sac to the developing lung buds as well as to the corresponding dorsal aorta, the latter being the main channel. Soon after formation of the sixth aortic arch, the outflow tract of the heart is divided by an influx of neural crest cells, which form the spiral aorticopulmonary septum ( ) that separates the aortic sac into the pulmonary trunk and ascending aorta. The part of the sixth aortic arch between the pulmonary trunk and the dorsal aorta is lost on the right but on the left becomes the ductus arteriosus which remains the main channel for blood to pass from the right ventricle to the descending aorta until the lungs and their associated blood vessels expand at birth. After birth, the ductus arteriosus is functionally closed by contraction of the circular muscle of the tunica media leaving a ligamentous remnant, the ligamentum arteriosum ( Ch. 13 ) (see Fig. 17.9 ). The right dorsal aorta caudal to the right subclavian artery also degenerates, leaving the left dorsal aorta as the definitive descending aorta (see Fig. 17.9 ).

Venous drainage of the pharyngeal arches and head

Blood returning from the early head flows into a close-meshed capillary plexus continuous cranially with a transitory primordial hindbrain channel that lies on the neural tube medial to the cranial nerve roots and later becomes the primary head vein. This vessel runs caudally from the medial side of the trigeminal ganglion, lateral to the facial and vestibulocochlear nerves and the otocyst, then medial to the vagus nerve, to become continuous with the precardinal vein and a lateral anastomosis subsequently brings it lateral to the vagus nerve (see Figs 13.1 , 13.17 ).

The ventral pharyngeal vein drains the mandibular and hyoid arches into the common cardinal vein ( Fig. 17.10A ) and with neck elongation into the cranial part of the precardinal vein, which later becomes the internal jugular vein ( Fig. 17.10B ). The ventral pharyngeal vein receives tributaries from the face and tongue, and becomes the linguofacial vein. As the face develops, the primitive maxillary vein extends its drainage into the territories of supply of the ophthalmic and mandibular divisions of the trigeminal nerve, including the pterygoid and temporal muscles, and it anastomoses with the linguofacial vein over the lower jaw. This anastomosis becomes the facial vein: it receives blood from the retromandibular vein from the temporal region, and drains through the linguofacial vein into the internal jugular vein. The stem of the linguofacial vein is now the lower part of the facial vein, whilst the dwindling connection of the facial with the primitive maxillary vein becomes the deep facial vein.

The external jugular vein develops from a tributary of the cephalic vein within the tissues of the neck and anastomoses secondarily with the anterior facial vein. At this stage, the cephalic vein forms a venous ring around the clavicle, by which it is connected with the caudal part of the precardinal vein. The deep segment of the venous ring forms the subclavian vein and receives the definitive external jugular vein. The superficial segment of the venous ring dwindles, but may persist minimally in adult life. The deep aspects of the maxillomandibular facial prominences, the retrogingival oral cavity, the pharyngeal walls and their lymphoid and endocrine derivatives, and the cervicothoracic oesophagus thus all have drainage channels that connect with the precardinal complex. Laryngeal and tracheobronchial veins also drain to the precardinal complex, whilst the capillary plexuses, developed in the (splanchnopleuric) walls of the fine terminal respiratory passages and alveoli, converge on pulmonary veins of increasing calibre, finally making secondary connections with the left atrium of the heart.

Pharyngeal ectoderm and clefts

Surface ectoderm lines the roof of the embryonic pharynx from the outer margin up to and including the invagination of the adenohypophysial (Rathke’s) pouch (see Figs 14.9 – 14.10 ). It also completely covers the first arch, including the lateral walls and floor of the stomodeum, unlike the more caudal arches, which are lined with endoderm. The external surface ectoderm of the first arch ultimately produces the keratinized stratified squamous epithelium of the epidermis, including hair follicles, sweat and sebaceous glands, and the specialized epithelium of the vermilion part of the lips. Within the oral cavity, first arch ectoderm forms the mucous membranes of the internal surface of the lips and cheeks, the palate, the presulcal part of the tongue, the epithelial components of the salivary and mucous glands, and the enamel organs of the developing teeth (see Figs 17.15 – 17.16 ). The first pharyngeal cleft is obliterated ventrally; its dorsal end deepens to form the external acoustic meatus, including its ceruminous glands and the outer surface of the tympanic membrane (see Fig. 17.4 ). Developmental studies of gene expression in the pharyngeal arches in chick and mouse embryos are calling into question the traditional view of pharyngeal cleft development based on external appearance. In mouse embryos the external acoustic meatus forms more rostrally from an invagination of the ectoderm of the first arch rather than at the first pharyngeal cleft ( ; ). Three auricular hillocks are observed on the first and second arches each side of the first pharyngeal cleft, during stages 15–16. It was thought that these contributed equally to the auricle (pinna) of the external ear, however, 3D reconstruction in human embryos up to stage 23 has shown that cells from the second arch form almost the entire auricle, whereas the first arch ectoderm and mesenchyme give rise to the tragus and anterior part of the external auditory meatus ( ) ( Ch. 16 ).

The external contours of the arches and clefts are modified as the skeletal and muscular elements develop. During stages 18–19 the second, third and fourth pharyngeal clefts form the rostral and caudal parts of a depression, the cervical sinus. As shown in Fig. 17.4 , the sinus is adjacent to extensions from the occipital myotomes that contribute to sternocleidomastoid, trapezius and platysma. Fusion of the hyoid arch with the cardiac elevation closes the cervical sinus, excluding the third, fourth and sixth arches from contributing to the skin of the neck and also results in platysma, which lies within the superficial fascia, extending along the neck to the ventral thoracic wall.

Pharyngeal endoderm and pouches

The four pharyngeal pouches appear in sequence craniocaudally during stages 10–13. The rostral pharynx is broad and dorsoventrally compressed (see Fig. 17.19 ). Laterally, the endoderm of the pouches approaches the ectoderm of the pharyngeal clefts to form thin closing membranes (see Fig. 17.4 ). The approximating ectoderm and endoderm between the first cleft and pouch form the outer and inner surfaces of the tympanic membrane. The ventral end of the first pouch is obliterated, but its dorsal end persists and expands as the head enlarges. This, together with the adjoining lateral part of the pharynx, and possibly with a contribution from the dorsal part of the second pharyngeal pouch, constitutes the tubotympanic recess. The recess forms the middle ear cavity, the pharyngotympanic tube and epitympanic recess. Expansion of the middle ear cavity around the ear ossicles occurs late during fetal life, by breakdown of the mesenchyme around the ossicles so that the cavity comes to surround them, except at their attachments to the tympanic membrane and fenestra ovalis (fenestra vestibuli, oval window).

The ectoderm of the pharyngeal clefts and the endoderm of the pouches become increasingly separated by mesenchyme. The blind recesses of the second, third and fourth pouches are prolonged dorsally and ventrally as angular, wing-like diverticula (see Fig. 17.19 ) and the pouch endoderm thickens and evaginates into localized neural crest-derived mesenchymal condensations. Further development of the second, third and fourth pouches is summarized in Fig. 17.19 and described in the associated text.

Face

By stage 12 migration of the most rostral neural crest cell population is complete and the sequence of morphogenetic changes that will form the face begins ( Fig. 17.11 ). Neural crest cells have populated the mandibular arch and its maxillary extension, and formed the frontonasal mesenchyme that covers the telencephalon and caudal diencephalon (see Fig. 17.2 ). They also contribute to the primordium of the trigeminal nerve, whose first fibres begin to extend at stage 13. The three divisions of the trigeminal nerve will provide sensory innervation to the frontonasal, maxillary and mandibular parts of the face, respectively.

Localized mesenchymal proliferation results in the formation of four paired processes, namely the medial and lateral nasal, maxillary and mandibular processes. The lateral and medial nasal processes surround the nasal placodes, causing them to sink deep to the surface, forming the nasal pits. The two medial nasal processes approach each other to form the nasal septum between them and extend downwards to form the premaxillary component of the upper lip and jaw and the primary palate. Concomitant with formation of the nasal processes, proliferation of the maxillary mesenchyme forms the maxillary processes that make contact with the medial and lateral nasal processes at stages 16–17 (see Fig. 17.11 ). Fusion of the maxillary processes with the medial nasal processes unites the premaxillary and maxillary parts of the upper jaw and lip; failure of this process on one or both sides causes unilateral or bilateral cleft lip (see Fig. 17.18 ). Superiorly, this fusion closes the cleft at the lower edge of the nasal pits, completing the future nostrils. Fusion of the maxillary with the lateral nasal processes is a much simpler process and rarely gives rise to anomalies. At stage 16 the epithelium of the groove between these fusing processes thickens to form the lacrimal lamina, the primordium of the nasolacrimal system. At stage 19 it separates from the surface ectoderm, forming the lacrimal cord beneath the surface. The cord becomes canalized to form the nasolacrimal duct in postfertilization week 10 ( ). The original site of the lacrimal lamina marks the lateral division between frontonasal and maxillary contributions to the face: the sensory nerve supply of these territories is from the ophthalmic and maxillary divisions of the trigeminal nerve, respectively ( Fig. 17.12 ).

At the start of facial development, the stomodeal opening extends across the whole width of the embryonic head. A wide mouth is maintained until differential growth brings the eyes and the lateral parts of the maxillary–mandibular structures from the sides to the front of the face in stages 20–23. Although differential growth makes the mouth opening proportionately smaller, progressive fusion of the lateral regions of the maxillary and mandibular processes also makes an important contribution to decreasing the width of the mouth and to forming the cheeks. Differences in mouth width within the human population are mainly due to variation in the extent of maxillomandibular fusion. The period from stages 18 to 22 is the final period of major morphogenetic change in facial development. In addition to formation of the mouth and cheeks, it is marked by further narrowing of the nasal region and philtrum, and the ascent of the ears. By stage 19 the face is recognizably human, although differential growth will continue to bring about changes in proportion and the relative position of the features. (For further reading about the genetics of normal-range variation in facial morphology see , .)

The contribution made by the frontonasal process to surface epithelial derivatives extends from the skin of the forehead, over the supraorbital and glabellar regions, including the upper eyelid and conjunctiva, to the external aspect of the nose and philtrum of the upper lip. During later development, the maxillary nerve invades the skin of the philtrum and nasal alae, so that the trigeminal nerve distribution does not completely coincide with the tissue origins (compare Figs 17.11 and 17.12 ). A detailed 3D reconstruction of a stage 23 human embryo reported heterochronous skeletal muscle development: genioglossus, hyoglossus and styloglossus and all the extraocular muscles except levator palpebrae superioris were identified ( ).