Embryology of the Head, Face and Oral Cavity Raj Gopalakrishnan B.D.S., Ph.D. Oral and Maxillofacial Pathology Dept. of Diagnostic and Biological Sciences University of Minnesota School of Dentistry

Prenatal Development Figure from Ten Cate’s Oral Histology, Ed., Antonio Nanci, 6th edition

Differentiation of the Morula into Blastocyst Figure from Ten Cate’s Oral Histology, Ed., Antonio Nanci, 6th edition

Formation of Two-Layered Embryo (2nd week of gestation) Called bilaminar germ disk Ectoderm Endoderm Pre/prochordal plate Firm union between ectodermal and endodermal cells occur at prechordal plate Figures obtained from “Before We Were Born; Moore and Persaud, 6th edition, 2003”.

Formation of Three-Layered Embryo: Gastrulation (3rd week) Triploblastic embryo Figure from Ten Cate’s Oral Histology, Ed., Antonio Nanci, 6th edition

Formation of Three-Layered Embryo: Gastrulation (3rd week) Figures obtained from “Before We Were Born; Moore and Persaud, 6th edition, 2003”.

First 3 weeks: Leads to formation of triploblastic embryo Next 3-4 weeks: differentiation of major tissues and organs includes head and face and tissues responsible for teeth development differentiation of nervous tissue from ectoderm differentiation of neural crest cells (ectoderm) differentiation of mesoderm folding of the embryo (2 planes-rostrocaudal and lateral)

Formation of neural tube and neural groove Neural tube undergoes massive expansion to form the forebrain, midbrain and hindbrain Figures obtained from “Before We Were Born; Moore and Persaud, 6th edition, 2003”.

Components of the mesoderm Along the trunk paraxial mesoderm breaks up into segmented blocks called somites Each somite has: sclerotome- 2 adjacent vertebrae and disks myotome-muscle dermatome-connective tissue of the skin over the somite In the head region the paraxial mesoderm only partially fragments to form a series of numbered somatomeres which contribute to head and neck musculature Intermediate mesoderm: urogenital system Lateral plate mesoderm: connective tissue of muscle annd viscera; serous membranes of the pleura; pericardium and peritoneum; blood and lymphatic cells; cardiovascular and lympahtic systems, spleen and adrenal cortex. Figure from Ten Cate’s Oral Histology, Ed., Antonio Nanci, 6th edition

In the head, the neural tube undergoes massive expansion to form the forebrain, midbrain and hindbrain The hindbrain segments into series of eight bulges called rhombomeres which play an important role in development of the head

Folding of the Embryo Head fold forms a primitive stomatodeum or oral cavity; leading to ectoderm lining the stomatodeum and the stomatodeum separated from the gut by buccopharyngeal membrane Onset of folding is at 24 days and continues till the end of week 4 Embryo just before folding (21 days) Figure from Ten Cate’s Oral Histology, Ed., Antonio Nanci, 6th edition

Figure from Ten Cate’s Oral Histology, Ed., Antonio Nanci, 6th edition

Neural Crest Cells Group of cells separate from the neuroectoderm, migrate and differentiate extensively leading to formation of cranial sensory ganglia and most of the connective tissue of the head Embryonic connective tissue elsewhere is derived form mesoderm and is known as mesenchyme But in the head it is known as ectomesenchyme because of its origin from neuroectoderm Look up Fig 2-12 in text book for derivative of the germ layers and neural crest

Avian neural crest cells Figure from Ten Cate’s Oral Histology, Ed., Antonio Nanci, 6th edition

Head Formation (one of the first are the occipital somites) Rhombomeres Figure from Ten Cate’s Oral Histology, Ed., Antonio Nanci, 6th edition

Neural Crest Cell Migration Figure from Ten Cate’s Oral Histology, Ed., Antonio Nanci, 6th edition

Pharyngeal arches expand by proliferation of neural crest cells Forebrain (prosencephalon) Midbrain (mesencephalon) r3 Hindbrain (rhombencephalon) r5 Couly et al., 2002

Migration of cranial neural crest cells Anterior midbrain FNM E TG Posterior midbrain E TG Md Anterior hindbrain E TG Md Imai et al., 1996

Clinical Correlation Treacher Collins Syndrome is characterized by defects of structures that are derived form the 1st and 2nd branchial arches and is due to failure of neural crest cells to migrate properly to the facial region

Sagittal section through a 25-day embryo Buccopharyngeal membrane ruptures at 24 to 26 days Sagittal section through a 25-day embryo Figure from Ten Cate’s Oral Histology, Ed., Antonio Nanci, 6th edition

Internal View of the Oral Pit at 3.5 weeks

26-day embryo Figure from Ten Cate’s Oral Histology, Ed., Antonio Nanci, 6th edition

The pharyngeal apparatus groove/cleft pouch arch membrane esophagus The pharyngeal apparatus 1 2 3 4 Branchial arches form in the pharyngeal wall (which has lateral plate mesoderm sandwiched between ectoderm and endoderm) as a result of lateral plate mesoderm proliferation and subsequent migration by neural crest cells The Developing Human by Moore & Persaud

3 weeks

Sagittal view of the branchial arches with corresponding grooves between each arch. Pharyngeal pouches are seen in the wall of the pharynx. The aortic arch vasculature leads from the heart dorsally through the arches to the face

Fate of the Pharyngeal Grooves and Pouches First groove and pouch: external auditory meatus tympanic membrane tympanic antrum mastoid antrum pharyngotympanic or eustachian tube 2nd, 3rd and 4th grooves are obliterated by overgrowth of the second arch forming a cervical sinus – if persists forms the branchial fistula that opens into the side of the neck extending form the tonsillar sinus 2nd pouch is obliterated by development of palatine tonsil 3rd pouch: dorsally forms inferior parathyroid gland ventrally forms the thymus gland by fusing with the counterpart from opposite side

4th pouch: dorsal gives rise to the superior parathyroid gland ventral gives rise to the ultimobranchial body (which gives rise to the parafollicular cells of the thyroid gland) 5th pouch in humans is incorporated with the 4th pouch

(A) Tissue from arch II and V growing towards each other (arrows) to make branchial arches and grooves disappear (B) Resulting appearance following overgrowth (C) Contribution of each pharyngeal pouch

Anatomy of the Branchial Arches Cartilage of 1st arch: Meckel’s Cartilage of 2nd arch: Reichert’s Other arches not named Some mesenchyme around cartilage gives rise to striated muscle Each arch also has an artery and nerve Nerve: two components (motor and sensory) Sensory nerve divides into 2 branches: Posttrematic branch: covers the anterior half of the arch epithelium Prettrematic: covers the posterior half of the arch epithelium Figures obtained from “Before We Were Born; Moore and Persaud, 6th edition, 2003”.

Meckel’s cartilage: Has a close relationship with the developing mandible BUT DOES NOT CONTRIBUTE TO IT Indicates the position of the future mandible. The mandible develops by intramembranous ossification. The malleus and the incus develop by endochondral ossification of the dorsal aspect of this cartilage. Innervation: V cranial nerve Reichert’s: Dorsal end: stapes and styloid process Ventral end: lesser horns of hyoid bone and superior part of the body of the hyoid bone Innervation: VII cranial nerve Cartilage of the 3rd arch: inferior part of the body and greater horns of the hyoid bone Cartilage of 4th and 6th arches: fuse to form the laryngeal cartilage

Table obtained from “Before We Were Born; Moore and Persaud, 6th edition, 2003”.

Aortic Vasculature Development At 4 weeks the anterior vessels have passed through each branchial arch tissue and have disappeared. The pouches project laterally between each arch. At 5 weeks the 3rd branchial arch vessel becomes the common carotid, which supplies the face by means of the internal carotid and stapedial arteries. Face, Neck and Brain are supplied by the common carotid through internal carotid. But by 7 weeks the circulation of face and neck shifts from the internal carotid to external carotid. The internal carotid continues to supply the brain.

Details of the aortic arch changes during early development Details of the aortic arch changes during early development. Aortic arch vessels numbers 1,2 and 5 disappear . Arch 3 becomes the common carotid artery. Arch 4 becomes the dorsal aorta and enlarges so that the common carotid arises from the aorta. Arch 6 becomes the right and left pulmonary arteries

Shift in the vascular supply to the face Face and brain are supplied first by the internal carotid artery Facial vessels detach from the internal carotid and attach to the external carotid

Muscle cells in the first arch become apparent during the 5th week and begin to spread within the mandibular arch into each muscle site’s origin in the 6th and 7th week. These form the muscles of mastication – masseter, medial pterygoid, lateral pterygoid and temporalis muscle. They all relate to the developing mandible By 7 weeks the muscles of 2nd arch grow upward to form the muscles of face. As these muscles grow and expand they forms sheet over the face and forms the muscles of facial expression

Masticatory muscles of the mandibular arch Facial muscles grow from the 2nd branchial arch to cover the face, scalp and posterior to the ear

Cranial Nerves growing into Branchial Arches

Cartilages derived from the branchial arches Arch 1: Meckel’s cartilage and incus Arch 2: Stapes, stylohyoid and lesser hyoid Arch 3: Greater hyoid Arch 4 and 6 thyroid and laryngeal cartilage

Anomalies of the head and neck Congenital auricular sinuses and cysts Branchial cysts Branchial sinuses Branchial fistula Branchial vestiges (cartilaginous or bony remnants) Dermatlas Dermatlas

Apparent fusion of facial processes by elimination of furrows True fusion of facial processes by breakdown of surface epithelium Figure from Ten Cate’s Oral Histology, Ed., Antonio Nanci, 6th edition

Development of the Face The face develops between the 24th and 38th days of gestation On 24th day, the 1st branchial arch divides into maxillary and mandibular arches Figures obtained from “Before We Were Born; Moore and Persaud, 6th edition, 2003”.

Frontonasal process Figures obtained from “Before We Were Born; Moore and Persaud, 6th edition, 2003”.

Figures obtained from “Before We Were Born; Moore and Persaud, 6th edition, 2003”.

Figures obtained from “Before We Were Born; Moore and Persaud, 6th edition, 2003”.

Formation of the Lips Middle portion of the upper lip: Formed by the fusion of the medial nasal process of both sides along with the frontonasal process Lateral portion of the upper lip: Fusion of the maxillary processes of each side and medial nasal process Lower lip: Formed by the fusion of the two mandibular processes Unusual fusion between maxillary process and lateral nasal process leading to canalization and formation of the nasolacrimal duct

Human embryo at 7 weeks Figure from Ten Cate’s Oral Histology, Ed., Antonio Nanci, 6th edition

Cleft Lip

Pituitary Gland Development Ectodermal in origin and develops from 2 sources: An upgrowth from the ectodermal roof of the stomatodeum called hypophysial diverticulum (Rathke’s Pouch) - adenohypophysis A downgrowth from the neuroectoderm of the diencephalon called the neurohypophysial diverticulum – neurohypophysis During the 4th week of development, a hypophysial diverticulum (Rathke’s pouch) projects from the roof of the stomatodeum and lies adjacent to the floor (ventral wall) of the diencephalon. By the 5th week, this pouch has elongated and has become constricted at its attachment to the oral epithelium and is in contact with the infundibulum (derived from the neurohypophysis)

Figures obtained from “Before We Were Born; Moore and Persaud, 6th edition, 2003”.

Figures obtained from “Before We Were Born; Moore and Persaud, 6th edition, 2003”.

Derivation and Terminology of the Pituitary Gland Oral Ectoderm Adenohypophysis Pars distalis (hypophysial diverticulum (glandular portion) Pars tuberalis from roof of stomodeum) Pars intermedia Neuroectoderm Neurohypophysis Pars nervosa (neurohypophysial (nervous portion) Infundibular stem diverticulum from Median eminence floor of diencephalon) Clinical Significance: Craniopharyngiomas develop from remnants of stalk of hypophysial diverticulum (in pharynx of sphenoid bone)

Formation of the palate (weeks 7 to 9) Palate develops from the primary palate and the secondary palate The primary palate develops at about 28 days of gestation Primary palate develops from the frontonasal and medial nasal processes and eventually forms the premaxillary portion of the maxilla The secondary palate develops between 7th and 8th week of gestation and completes in the 3rd month The critical period of palate development is from the end of 6th week till the beginning of 9th week

Formation of the secondary palate (starts between 7 to 8 weeks and completed around 3 months) Figure from Ten Cate’s Oral Histology, Ed., Antonio Nanci, 6th edition

Figure from Ten Cate’s Oral Histology, Ed., Antonio Nanci, 6th edition

Cleft Palate

Formation of the Tongue The tongue begins to develop at about 4 weeks. The oral part (anterior two-thirds) develops from two distal tongue buds (lateral lingual swellings) and a median tongue bud (tuberculum impar) [1st branchial arch]. Innervation: V nerve The pharyngeal part develops from the copula and the hypobranchial eminence [2nd, 3rd and 4th branchial arches]. Innervation: IX cranial nerve The line of fusion of the oral and pharyngeal parts of the tongue is roughly indicated in the adult by a V-shaped line called the terminal sulcus. At the apex of the terminal sulcus is the foramen cecum. Muscles of the tongue develop form the occipital somites and innervated by hypoglossal nerve

Lingual swelling Tuberculum impar Figures obtained from “Before We Were Born; Moore and Persaud, 6th edition, 2003”.

The lingual papillae appear by the end of 8th week Vallate and foliate papillae appear first, fungiform and filiform (10-11 weeks) papillae appear later Taste buds develop during the 11 to 13 weeks by inductive interaction between epithelial cells of the tongue and invading gustatory nerve cells from chorda tympani, glossopharyngeal and vagus nerves

Thyroid gland development (4 to 7 weeks) Figures obtained from “Before We Were Born; Moore and Persaud, 6th edition, 2003”.

Lingual thyroid Thyroglossal duct cyst

Development of Jaw Bones Figure from Ten Cate’s Oral Histology, Ed., Antonio Nanci, 6th edition

Development of Mandible Figure from Ten Cate’s Oral Histology, Ed., Antonio Nanci, 6th edition

Figure from Ten Cate’s Oral Histology, Ed., Antonio Nanci, 6th edition

Figure from Ten Cate’s Oral Histology, Ed., Antonio Nanci, 6th edition

Fate of Meckel’s Cartilage Posterior – malleus of the inner ear Sphenomandibular ligament Anteriorly, may contribute to mandible by endochondral ossification (some evidence) Rest are resorbed completely

Secondary Cartilages Three secondary (growth) cartilages govern further growth of mandible until birth Condylar cartilage (most important) Coronoid cartilage Symphysial cartilage

Appears during 12th week and occupies most of the ramus and is quickly ossified by endochondral ossification, with a very thin layer of cartilage present in the condylar head. This remnant persists until 2nd decade of life and is important for growth of mandible Appears at 4 months and disappears immediately Figure from Ten Cate’s Oral Histology, Ed., Antonio Nanci, 6th edition

Development of Maxilla Develops from one center of ossification in maxillary process of the 1st branchial arch Center of ossification is angle between the divisions where the anterosuperior dental nerve is given off from inferior orbital nerve from where it spreads posteriorly, anteriorly and superiorly No arch cartilage is present, so maxilla develops in close association with the nasal cartilage One secondary cartilage also contributes to maxilla development: zygomatic cartilage