1. Prof Marina Kapitonova HEAD AND NECK. DEVELOPMENT, DEFECTS and MALFORMATIONS. Lecture for the Year 2 Dental Students

3. Primodia for the Head and Neck region: -mesoderm (paraxial and lateral plate mesoderm) -ectoderm (neural tube, neural crest, ectodermal placodes) -endoderm (pharyngeal pouches originating from the pharyngeal gut – the cephalic part of the foregut)

4. Early development of the Embryo. Folding of the embryonic disc. Middle of the 3rd week – presomite stage, pan-cake appearance of embryonic disc, i ntraembryonic endoderm constitutes the roof of the spherical yolk sac. Endoderm Ectoderm Angiogenic cell cluster Prechordal plate Amniotic cavity Connecting stalk Allantois Cloacal membrane

7. A :Formation and migration of neural crest cells in the spinal cord. B: crest cells form at the tip of neural fold

8. Stage 9 Appearance of Somites 1.5 - 2.5 mm 19 - 21 days post-ovulation By stage 9 the embryo from a top view resembles the sole of a shoe with the head end wider than the tail end, and a slightly narrowed middle. The first pair of somites appear at the tail and progress to the middle. One to three pairs of somites are present by Stage 9. Human embryo, 3 weeks old

12. Embryonic Development of the Heart, Days 21-23 . Stage 10 reflects rapid growth and change as the embryo becomes longer and the yolk sac expands. On each side of the neural tube, between four and twelve pairs of somites can exist by the end of Stage 10.

13. Formation of somites (segmented blocks) at beginning of the 3 rd week from paraxial mesoderm

14. Differentiation of somites into ventromedial sclerotome and dorsolateral dermatomyotome with subsequent ventral extension of the myotome . Dorsal aorta sclerotome dermomyotome Neural tube sclerotome dermatome myotome Neural groove ventral somite wall notochord coelom sclerotome Neural tube Dorsal aorta

17. Mesenchyme of the Head and Neck regions originates from the: 1) paraxial mesoderm (somites) – forming - the floor of the brain case - small portion of the occipital region - all the voluntary muscles of the craniofacial region, -dermis and the connective tissue of the dorsal region of the head, -meninges caudal to the prosencephalon.

18. Skeletal structures of the Head and Face. Blue – mesenchyme derived from the neural crest; yellow – from the lateral plate, red – paraxial mesoderm (somites) Mesenchyme of the head region is derived from the paraxial and lateral plate mesoderm, neural crest and thickened regions of ectoderm known as ectodermal placodes. Paraxial mesoderm (somites) form the floor of the brain case and a small portion of the occipital region, all voluntary muscles of the craniofacial region and dermis and the connective tissue in the dorsal region of the head and the meninges caudal to the prosencephalon. Lateral plate forms the laryngeal cartilages (arytenoids and crycoid) and connective tissue of the region.

19. Mesenchyme of the Head and Neck regions originates from the: 2) lateral plate forming the laryngeal cartilages (arytenoids and crycoid) and connective tissue of the region; 3) neural crest (forming midfacial and pharyngeal arch skeletal structures and all the tissue in the region – cartilage, bone, dentin, tendon, dermis, pia, arachnoid, sensory neurons, glandular stroma) 4) Cells from the ectodermal placodes together with the neural crest from the neurons of the 5 th , 7 th , 9 th , 10 th cranial sensory ganglia. Migration pathways of the neural crest cells from the fore, mid-, hindbrain into the final location (shaded) in the face and pharyngeal arches. Ectodermal placodes assist the crest cells to form the 5 th , 7 th , 9 th and 10 th cranial sensory ganglia.

21. Similtaneously with development of the arches and clefts a number of outpocketings, the pharyngeal pouches, appear along the lateral walls of the pharyngeal gut, the most cranial part of the foregut (each arch contains a cartilaginous component, a cranial nerve, and artery and a muscular component). The pouches penetrate the surrounding mesenchyme but do not establish an open communication with the external clefts Hence, though development of the arches, pouches and clefts resembles formation of gills in fishes. In human embryo real gills (brachia) are never formed. Therefore the term pharyngeal (arches, clefts, pouches) has been adopted for the human embryo. Pharyngeal Arches

22. a. Frontal view of the embryo 24 days old. The stomodeum is closed by the buccopharyngeal membrane and is surrounded by the 5 mesenchymal prominences. b. Embryo at 1 month. Rupture of the buccopharyngeal membrane and formatin of he nasal placodes on the fromtonasal prominence. Pharyngeal arches are important for neck and face development. At the end of the 4 th week the center of the face is formed by stomodeum surrounded by the 1 st pair of the pharyngeal arches. In 4-week old embryo 5 mesenchymal prominences can be recognized: the mandibular prominences (1 st arch), caudal to stomodeum; the maxillary prominences (dorsal portion of the 1 st pharyngeal arch), lateral to stomodeum; and the frontonasal prominence, a slightly rounded elevation cranial to the stomodeum.

23. Each pharyngeal arch consists of a core of mesenchymal tissue covered on the outside by surface ectoderm and on the inside by endodermal epithelium. In addition to mesenchyme derived from paraxial and lateral mesoderm, the core of each arch receives substantial numbers of neural crest cells, which migrate into the arches to contribute to the skeletal components of the face. The original mesoderm of the arches gives rise to the musculature of the face and neck. Thus each pharyngeal arch is characterized by its own muscular component. PHARYNGEAL ARCHES

24. The muscular components of each arch have their own cranial nerve, and wherever the muscle cells migrate, they carry their nerve component with them. Nerve supply of the pharyngeal arches

25. In addition each arch has its own arterial component . Pharyngeal pouches as outpocketings of the foregut and the primodium of the thyroid gland and aortic arches).

26. Derivatives of the Pharyngeal arches pharyngeal arch nerve muscles skeleton 1.Mandibular (maxillary and mandibular processes) V.Trigeminal (maxillary and mandibular divisions Mastification (temporal; masseter; medial, lateral pterygoids); mylohyoid; anterior belly of digastrics; tensor palatine, tensor tympani Premaxilla, maxilla, zygomatic bone, part of the temporal bone, Meckel’s cartilage, mandible malleus, incus, anterior ligament of malleus, sphenomandibular ligament 2.Hyoid VII.Facial Facial expression (buccinator, auricularis, frontalis, platisma, orbicularis oris, orbicularis oculi); posterior belly of digastrics; stylohyoid; stapedius Stapes; styloid process; stylohyoid ligament; lesser horn and upper portion of body of hyoid bone 3. IX.Glossopharyngeal Stylopharyngeus Greater horn and lower portion of the body of the hyoid bone 4-6 X.Vagus – superior laryngeal branch (nerve to 4 th arch. Recurrent laryngeal branch (nerve to 6 th arch) Cricothyroid; levator palatine; constrictors of pharynx Intrinsic muscles of larynx Laryngeal cartilages (thyroid, cricoids, arytenoids, corniculate, cuneiform)

27. 1 st arch consists of a dorsal portion, the maxillary process, which extends forward beneath the region of the eye, and a ventral portion, the mandibular process, which contains Merckel’s cartilage. Maxillary process and Merckel’s cartilage are replaced by the maxilla and mandible respectively which develop by membranous ossification. … Lateral view of the head and neck in 4-week embryo: cartilages of the arches forming the bones of face and neck

28. Merckel’s cartilage will later disappear except for 2 small portions at its dorsal end that persists and form incus and malleus . Mesenchyme of the maxillary process gives rise to premaxilla, maxilla, zygomatic bone and part of temporal bone through membranous ossification . The mandible is also formed by membranous ossification of the mesenchyme around the Merckel’s cartilage. Various components of the pharyngeal arches later in development. Some of the components ossify, others disappear and become ligamentous.

29. Definite structures formed by the cartilaginous components of the arches. In addition the 1 st arch contributes to formation of the bones of the middle ear.

30. Masculature of the 1 st arch includes: muscles of mastication (temporalis, masseter, pterygoids), anterior belly of the digastrics, mylohyoid, tensor tympani, tensor palatini supplied by the mandibular branch of the CN5. Since mesenchyme from the 1 st arch also contributes to the dermis of the face, sensory supply to the skin of the face is provided by the ophthalmic, maxillary and mandibular branches of the trigeminal nerve. Muscles of the arches do not always attach to the bony or cartilagenous components of their own arch but sometimes migrate into surrounding regions. Nevertheless, the origin of these muscles can always be traced, since the nerve supply is derived from the arch of the origin.

31. 2 nd arch. The cartilage of the 2 nd arch (hyoid) (Reicher’s cartilage) gives rise to the stapes, styloid process of the temporal bone, stylohyoid ligament and ventrally to lesser horn and upper part of the body of the hyoid bone. Muscles of the 2 nd arch: stapedius, stylohyoid, posterior belly of the digastrics, auricular, muscles of the facial expression, they are all supplied by the facial nerve. 3 rd arch’s cartilage produces lower part of the body and greater horn of the hyoid

32. The musculature is limited to the stylopharyngeus muscles innervated by the glossopharyngeal nerve.

33. 4 th and 6 th arches’ cartilaginous components fuse to form thyroid, cricoids, arytenoids, corniculate and cuneiform cartilages of the larynx . Muscles of the 4 th arch (crycothyroid, levator palatine, constrictors of the pharynx) are innervated by the superior laryngeal branch of the vagus. Intrinsic muscles of the larynx are supplied by the recurrent laryngeal branch of the vagus, the nerve of the 6 th arch.

34. Pharyngeal pouches. The human embryo has 5 pairs of pouches. The last one of these is atypical and often considered as part of the 4 th . Epithelial endodermal lining of the pouches gives rise to a number of organs. 1 st pouch . The 1 st pouch form a stalk-like diverticulum, the tubotympanic recess, which comes in contact with the epithelial lining of the 1 st cleft, the future external auditory meatus. The distal portion of the diverticulum widens into a saclike structure, the primitive tympanic or middle ear cavity, and the proximal part remains narrow, forming the auditory (Eustachian) tube. The lining of the tympanic cavity later aids in formation of the tympanic membrane or eardrum. Pharyngeal Pouches

35. 2 nd pouch . The epithelial lining of the 2 nd pouch proliferates and forms buds that penetrate into the surrounding mesenchyme. The buds are secondarily invaded by mesenchymal tissue, forming the primodium of the palatine tonsil. During the 3 rd and the 5 th month the tonsil in infiltrated by the lymphoid tissue. Part of the pouch remains and is found in the adult as the tonsillar fossa. 3 rd pouch. The 3 rd and the 4 th pouches are characterized as their distal extremity by a dorsal and ventral wing.In the 5 th week epithelium of the dorsal of the 3 rd pouch differentiates into the inferior parathyroid glands while the ventral wing forms the thymus. 2 nd and 3 rd pouches

36. Migration of the thymus, parathyroid glands and ultimobranchual body. ultimibranchial bodies thymus thyroid superior parathyroid (from 4 th pouch inferior parathyroid (from 3rd pouch foregut Foramen cecum palatine tonsil auditory tube primitive tympanic cavity 6 weeks Both gland primodia loose their connection with a pharyngeal wall and the thymus then migrates to caudal and medial direction, pulling the inferior parathyroid with it Although the main portion of the thymus moves rapidly to its final position in the anterior part of the thorax, where it fuses with its counterpart from the opposite side, its tail portion sometime persists either embedded in the thyroid gland or as isolated thymic nests.

37. Growth and development of the thymus continue until puberty. In the young child the thymus occupies considerable space in the thorax and lies behind the sternum and anterior to the pericardium and great vessels. In older persons it is difficult to recognize, since it is atrophied and replaced by fatty tissue. DEVELOPMENT OF THYMUS

38. The parathyroid tissue of the 3 rd pouch finally continues to rest on the dorsal surface of the thyroid gland and forms the inferior parathyroid gland 4 th pouch. Epithelium of the dorsal wing of the 4 th pouch forms the superior parathyroid gland. When it loses contact with the wall of the pharynx, it attaches itself to the dorsal surface of the caudally migrating thyroid as the superior parathyroid gland. 3 rd and 4 th Pouches

39. . Development of thymus Maxillary process Mandibular process Pharyngeal clefts External auditory meatus Palatine tonsil Parathyroid gland inferior Thymus Parathyroid gland superior Pharyngeal pouches 5 th pouch. It is usually considered as a part of the 4 th pouch, it is the last to develop. It gives rise to the ultimobranchial body which is later incorporated into the thyroid gland. Cells of the ultimobranchial body give rise to the C-cells of the thyroid gland secreting calcitonin.

40. The 5-week embryo is characterized by the presence of the 4 clefts of which only one contributes to the definite structure of the embryo. The dorsal part of the 1 st cleft penetrates the underlying mesenchyme and gives rise to the external auditory meatus. The epithelial lining at the bottom of the meatus participates in the formation of the eardrum. Active proliferation of the mesenchyme in the 2 nd arch causes it to overlap the 3 rd and the 4 th arches. Finally it merges with the epicardial ridge in the lower part of the neck, and the 2 nd , 3 rd , 4 th clefts lose contact with the outside. The clefts form a cavity lined with ectodermal epithelium, the cervical sinus, but with further development this sinus disappears. Pharyngeal clefts.

41. DEVELOPMENT OF THE TONGUE Stage 12. Day 26-27 floor of pharynx The tongue appears in 3 weeks as the two lateral lingual swelling and one medial swelling, the tuberculum impar, all originate from the 1 st pharyngeal arch. A 2 nd median swelling – the copola or hypobranchial eminence, is formed by the mesoderm of the 2,3, and part of the 4 th arch. lingual swelling tuberculum impar foramen caecum copula= hypobrachial eminence laryngotracheal groove copola

42. The 3 rd median swelling formed by the posterior part of the 4 th arch marks development of the epiglottis. Behind this swelling is the laryngeal orifice which is flanked by the arytenoids swelling. DEVELOPMENT OF THE TONGUE foramen caecum hypobranchial eminence epiglottal swelling arytenoid swellings laryngotracheal groove

43. Development of the tongue. As the lateral lingual swellings increase in size they overgrow the tuberculum impar and merge, forming the anterior two-thirds of the tongue. Since mucosa of the body of the tongue originates from the 1 st arch, sensory innervations is by the mandibular branch of the trigeminal nerve. The posterior part of the tongue separated by sulcus terminalis originates from the 2 nd .3 rd and part of the 4 th arch. Tissue of the 3 rd arch overgrows that of the 2 nd , as a result sensory innervations is supplied by the glossopharyngeal nerve. Foramen cecum Body of tongue Epiglottis Arytenoid swellings Lingual swelling Epiglottal swelling Laryngeal orifice

44. Development of the tongue . The epiglottis and the extreme posterior part of the tongue are innervated by the superior laryngeal nerve reflecting its development from the 4 th arch. Most of the tongue muscles derive from the myoblasts of the occipital somites. Thus tongue muscles are innervated by the hypoglossal nerve. So, the sensory innervations: the body is supplied by the trigeminal nerve, the nerve of the 1 st arch; the root – by the glossopharyngeal and vagal nerves, the nerves of the 3 rd and 4 th arches respectively. Special sensory innervations (taste) to the anterior 2/3s is provided by chorda tympani branch of the facial nerve while the posterior third is supplied by the glossopharyngeal nerve. Tongue-tie (ankyloglossia) is a result of the failure of cells to degenerate at the floor of the mouth. That is why frenulum extends to the tip of the tongue and the tongue is not freed from the floor of the mouth. Foramen cecum Body of tongue Epiglottis Arytenoid swellings Lingual swelling Epiglottal swelling Laryngeal orifice

45. 5 th Pouch

46. DEVELOPMENT OF LARYNX The epiglottis is a derivative of the caudal part of the midline hypobranchial eminence which is produced by the proliferation of the 3 rd and 4 th branchial arch mesenchyme. As the mesenchyme proliferates, the epiglottal swelling and the two arytenoid swellings convert aditus from a linear to a T-shaped entrance. STAGE 16 37 th day, 11-14 mm STAGE 23 56 th day, 23-32 mm WEEK 10 epiglottal swelling primitive glottis arytenoid swelligs epiglottis cuneiform tubercle interarytenoid notch TONGUE TONGUE

47. CONGENITAL MALFORMATION OF THE PHARYNGEAL REGION 1.Ectopic thymic and parathyroid gland ( a result of migration of the glandular tissue derived from the pouches. (thymus may remain in the neck, parathyroid glands, especially inferior ones may remain at the bifurcation of the common carotid artery). 2.Branchial fistulas – provide drainage for a lateral cervical cysts which are the remnants of the cervical sinus, located on the lateral aspect of the neck anterior to the sternocleidomastoid muscle below the angle of the jaw. Often invisible at birth but later may grow and become prominent. They occur when the 2 nd arch fails to grow caudally over the 3 rd and 4 th arches thus leaving the remnants of the 2 nd , 3 rd and 4 th clefts in contact with the surface.

48. Thyroglossal duct may persist giving rise to the thyroglossal cysts . They may lie at any point along the migratory pathway of the thyroid gland but are always near or in the midline of the neck. Although approximately 50% of these cysts are close to or just inferior to the body of the hyoid bone, they may also be found at the base of the tongue or close to the thyroid cartilage. Sometimes a thyroglossal cyst is connected to the outside by a fistulous canal, a thyroglossal fistula. Such a fistula usually arises secondarily after rupture of a cyst but may be present at birth. Development of the Thyroid Gland – Clinical Correlations

49. Thyroglossal Cyst Thyroglossal cysts are the cystic remnants of the thyroglossal duct. They are commonly found behind the arch of the hyoid bone. An important diagnostic characteristic is their midline location. Thyroglossal cyst is a painless progressively enlarging movable mass. The cyst may contain some thyroid tissue.

51. Disturbances in the embryologic development of the thymus may give rise to a series of congenital anomalies and malformation. One of the most frequently encountered is the presence of parathyroid gland tissue within the thymus. Ectopic parathyroid tissue adjacent to normal thymic gland

52. Thymic anomalies. Di George Sequence (3 rd and 4 th pharyngeal pouch syndrome) – neural crest cells defect – includes hypoplasia or absence of thymus (crest cells contribute to the connective tissue of the gland), and/or parathyroid gland with or without CVS defects (persistent truncus arteriosus, interrupted aortic arch), abnormal external ears, micrognatia and hypotelorism (widely spaced eyes). Patients with complete DiGeorge sequence have immunological problems, hypocalciemia and poor prognosis. DiGeorge sequence occurs sporadically and may involve teratogens, such as the retinoids.

53. DiGeorge Syndrome Note hypotelorism and small jaw.

54. DiGeorge Syndrome Note abnormal ear. This child has an interrupted aortic arch.

55. Development of Nose C – during 5 th week they invaginate to form nasal pits. B – on both sides of frontonasal prominence nasal (olfactory) placodes originate under inductive influence of the forebrain, frontonasal prominence maxillary prominence mandibular prominence stomodeum heart prominence lens placode nasal placode stomodeum hyoid arch nasal pit eye nasolacrimal groove 24 +/- 1 day 28 +/- 1 day 31 +/- 1 day B C A A 1 B 1 C 1 branchial arches: 1 st 2 nd

56. Frontal view of a 4 ½-week old embryo. Nasal placodes are visible on either side of the frontonasal prominence. Development of Face in Human Embryo, SEM

57. DEVELOPMENT OF NOSE E – n asal pits are still two separate plates, but they rotate to face ventrally as head widens. D – a ridge of tissue around each nasal pit forms nasal prominences: medial and lateral. Lateral nasal and maxillary prominences are separated by nasolacrimal groove. After detachment of the cord forming naso-lacrimal duct, from the floor of the groove, the maxillary and lateral nasal prominences merge. nasal pit medial lateral nasal prominences nasolacrimal groove first branchial groove medial nasal prominence lateral nasal prominence external ear D E D 1 E 1 33 +/- 1 day 35 +/- 1 day

58. Development of Face in Human Embryo, SEM Frontal view of a 6-week old embryo. Nasal prominences are separated from the maxillary prominence by deep furrows.

59. In weeks 5-8 the maxillary prominences increase in size, and the medial nasal prominences move medially and merge to form the intermaxillary segment which includes nasal septum. As a result of medial growth of maxillary prominences the two medial nasal prominences merge not only at a surface but also at deeper level. Development of Nose eyelid nostril lower jaw eyelid medial nasal prominences merging with each other and maxillary prominences 40 +/- 1day 48 +/- 1day F F 1 G G 1

60. Development of Face in Human Embryo, SEM Frontal view of a 7-week old embryo. Maxillary prominences have fused with the medial nasal prominence.

61. Nose is formed from the 5 facial prominences: the frontal prominence gives rise to the bridge, the merged medial nasal prominences provide crest and tip, the lateral nasal prominences form the sides (alae). DEVELOPMENT OF NOSE nasolacrimal groove intermaxillary segment philtrum of lip H I H 1 I 1 10 weeks 14 weeks

62. Development of Nasal Cavities B – During 7 th week oro-nasal membrane ruptures bringing nasal and oral cavities into communication. A - During 6th week the nasal pits deepen considerably because of growth of nasal prominences and partly because of their penetration into underlying mesenchyme. It results in the formation of the primitive nasal sacs. Initially they are separated from the oral cavity by oro-nasal membrane. Wall of brain Nasal pit Medial nasal prominence Oronasal membrane Oral cavity Tongue Breakdown of oronasal membrane Oral cavity Tongue A B

63. Development of Nasal Cavities Nasal chamber Primitive choana Primary palate Maxilla Upper lip Lower lip Mandible Conchae Secondary palate Definitive choana C – in 7- week embryo the regions of continuity between nasal and oral cavities are primary choanae (openings between nasal cavity and nasopharynx). Primitive choanae are located on each side of midline behind the primitive palate formed by intermaxillary segment. C D – in 9- week embryo with formation of the secondary palate, separating oral and nasal cavities, and further development of nasal chambers, definite choanae are located at the junction of nasal cavity and nasopharynx. Ectodermal epithelium in the roof of each nasal cavity becomes specialized to form olfactory epithelium. D

65. Development of Secondary Palate Nasal septum Tongue Nasal chamber Palatine shelf Primary palate Nasal septum A – in 6-week embryo the two lateral outgrowths appear at the maxillary prominence. They are directed obliquely downward on each side of the tongue. A B – cleft between the primary palate and the palatine shelves. B

66. Development of Secondary Palate Nasal septum Oral cavity Tongue Palatine shelf Primary palate Eve Nasal chamber A – in the 7 ½ week embryo the palatine shelves ascend to attain a horisontal position above the tongue and fuse with each other forming the secondary palate. A B – the wedge-shaped median palatine process fuses with lateral palatine processes and the nasal septum. B

67. Development of Secondary Palate Bone gradually develops in the primary palate, formimg the premaxillary part of the maxilla. Bone formation in the anterior portion of the fused lateral palatine processes creates the hard palate. The palate posterior to the hard palate forms the soft palate and uvula. Nasal conchae Tongue Nasal chamber Nasal septum Fused palatal shelves Oral cavity Incisive foramen Uvula A – in 10 week embryo the two palatine shelves fuse with each other and with the nasal septum. The superior, middle and inferior conchae develop as elevations on the lateral walls of the nasal cavities. A B - the incisive foramen forms the midline between the primary and secondary palate. B

73. Photographs illustrating various types of cleft lip. A and B , Unilateral cleft lip. The cleft in B is Incomplete; the arrow indicators a band of tissue (Simonart’s band) connecting the cleft of the lip. C and D , Bilateral cleft lip. (Courtesy of Dr. D.A.Kernahan, The Children’s Memorial, Chicago.)

74. Photographs illustrating congenital anomalies of the lip and palate. A , Complete unilateral cleft of the lip and alveolar process. B , Complete bilateral cleft of the lip and alveolar process with bilateral cleft of the anterior palate. C and D , Bilateral cleft of the posterior or secondary palate; the lip is normal.