[EMBRYO]LEC_207_EMBRYONIC-DEVELOPMENT-OF-THE-HEAD-NECK-EYES-AND-EARS.pdf

(007) EMBRYONIC DEVELOPMENT OF THE HEAD, NECK, EYES, AND EARS DR. C. PANO | 01/25/21 OUTLINE...

(007) EMBRYONIC DEVELOPMENT OF THE HEAD, NECK, EYES, AND EARS DR. C. PANO | 01/25/21 OUTLINE 3. Auricle I. DEVELOPMENT OF PHARYNGEAL ARCHES XII. HEARING A. First Brachial Arch A. Clinical Correlation B. Second Brachial Arch 1. Hearing Loss and External Ear Abnormalities C. Third Brachial Arch 2. Risk Factors D. Fourth Brachial Arch B. Stapes E. Sixth Brachial Arch C. Externa; Ear Defects II. DEVELOPMENT OF THE FACE D. Periauricular Appendages and Pits III. DEVELOPMENT OF THE PARANASAL SINUSES XII. EYE IV. DEVELOPMENT OF PALATE A. Optic Cup and Lens Vesicle A. Development of Hard and Soft Palate B. Retina V. DEVELOPMENT OF JAWS C. Iris VI. DEVELOPMENT OF MANDIBLE D. Ciliary Body A. Pre-natal E. Lens B. Post-natal F. Choroid, Sclera, and Cornea VII. DEVELOPMENT OF MAXILLA G. Anterior Chamber A. Pre-natal H. Cornea B. Formation of Premaxilla I. Posterior Chamber VIII. DEVELOPMENT OF TEMPOROMANDIBULAR J. Pupil JOINT K. Vitreous Body IX. DEVELOPMENT OF TONGUE L. Optic Nerve A. Innervations M. Molecular Regulation of Eye Development X. DEVELOPMENT OF THE THYROID GLAND D. PAX6 XI. DEVELOPMENT OF TEETH E. SHH A. Molecular Regulation of Tooth Development N. Clinical Correlation XII. CLINICAL CORRELATIONS 1. Coloboma A. First Arch Anomalies 2. Congenital Cataract B. Second Arch Anomalies 3. Micropthalmia C. Third Arch Anomalies 4. Anopthalmia D. Fourth Arch Anomalies 5. Congenital Aphakia and Aniridia E. First Pouch Anomalies F. Second Pouch Anomalies G. Third and Fourth Pouch Anomalies H. Development Defects of the Salivary Glands I. Neural Crest Cells and Craniofacial Defects J. Tooth Abnormalities K. Tooth Abnormalities L. Facial Cleft XI. EAR A. Internal Ear 1. Otic Placodes 2. Otocyst 3. Cochlear Duct 4. Spiral Organ of Corti 5. 10th Week of Development 6. Semicircular Canals B. Middle Ear Figure 1. Skeletal Structures of the head and face. 1. Tympanic Cavity Ossicles C. External Ear 1. External Auditory Meatus 2. Eardrum or Tympanic Membrane Page 1 of 17 CMED 1D  (007) EMBRYONIC DEVELOPMENT OF THE HEAD, NECK, EYES, AND EARS DR. C. PANO | 01/25/21 region of the eye and the ventral portion the mandibular process which contains the Meckel’s cartilage. Measuring further development, this Meckel’s cartilage persists and form the incus and malleus in the mesenchyme of the maxillary process and later gives rise to pre-maxilla, maxilla and zygomatic bone and part of the temporal bone. A. FIRST BRACHIAL ARCH Divides early into 2 portions o Maxillary process dorsally (maxilla, zygoma, and squamous temporal bone through membranous ossification) o Mandibular process ventrally (also formed by membranous ossification of mesenchymal tissue surrounding Meckel’s Cartilage) Table 1. Derivatives of the Pharyngeal Arches and their Meckel’s Cartilage Innervation. o During further development, it disappears except for the small portions and its dorsal end I. DEVELOPMENT OF PHARYNGEAL becomes the malleus and incus ARCHES o Intermediate portion regresses but the perichondrium forms Derived from paraxial and lateral plate mesoderm and ▪ Anterior ligament of the malleus neural crest cells in the ventral part of the foregut ▪ Sphenomandibular ligament o Mesoderm-form muscle myoblast Ventral portion of the mandible o Neural crest cells- form skeleton and connective Muscular component tissue o Muscles of mastication (temporalis, masseter, Externally, separated by pharyngeal grooves and 5 medial and lateral pterygoids) pharyngeal pouches internally o Accessory muscles of mastication (mylohyoid, Each pharyngeal arch consists of central cartilage rod to anterior belly of digastric) form skeleton, muscular and vascular components and o Tensor tympani, tensor veli palatine nervous element o The nerve supply to the muscles of the first arch BRACHIAL APPARATUS is provided by the mandibular branch of the o 4 arches are well-developed by 4th week of trigeminal nerve. gestation o Because mesenchyme from the first arch also o 5th and 6th arches are still rudimentary contributes to the dermis of the face, sensory supply to the skin of the face is provided by ophthalmic, maxillary, and mandibular branches o Development takes place over 4-7 weeks of the trigeminal nerve. o Contribute mostly to neck development but the first arch contributes to facial development B. SECOND BRACHIAL ARCH o ARCHES-mesenchymal tissue surrounded by Reichert’s Cartilage ectoderm and endoderm o Dorsal end becomes stapes (except footplate) and o CLEFTS (or Grooves)- separate adjacent styloid process of temporal bone arches along ectodermal surface o Intermediate portion regresses and perichondrium forms o POUCHES-outpouching of endoderm from the stylohyoid ligament foregut; penetrate adjacent mesenchyme o Ventral end forms the lesser cornua of the hypoid and Pharyngeal arches are consist of core of mesenchymal the upper half of the hyoid bone tissue covered on the outside by surface ectoderm and in Muscular component the inside with epithelium of endodermal origin. each of these arches is characterized by its muscular o Migrates over superficial face to form the muscles of components, nerve component and arterial component. facial expression over first pharyngeal arch it consists of dorsal portion, o Stapedius, stylohyoid and posterior belly of digastric maxillary process which extends forward beneath the Page 2 of 17 CMED 1D  (007) EMBRYONIC DEVELOPMENT OF THE HEAD, NECK, EYES, AND EARS DR. C. PANO | 01/25/21 Aortic Arch Primitive tympanic or middle ear cavity, and the proximal part o Hyoid artery, stapedial artery remains narrow, forming the auditory (Eustachian tube). Nerve Lining of tympanic cavity later aids in formation of tympanic o Facial Nerve (CN VII), the nerve of the second arch, membrane or eardrum supplies all of these muscles. SECOND PHARYNGEAL POUCH Proliferates and forms buds that penetrate into the surrounding C. THIRD BRACHIAL ARCH mesenchyme Buds are secondarily invaded by mesodermal tissue, forming Cartilage the primordium of the palatine tonsils o Located ventrally and forms the lower half of the 3rd and 5th months, tonsil is infiltrated by lymphatic tissue. body of the hyoid and greater cornua Part of the pouch remains and found in the adult as the tonsillar Muscular component fossa o Stylopharyngeus THIRD PHARYNGEAL POUCH Aortic Arch 5th week, epithelium of the dorsal region of the third pouch o Common, external and proximal internal carotid differentiates into the inferior parathyroid gland Nerve Ventral region form the thymus o Glossopharyngeal Nerve (CN IX), the nerve of FOURTH PHARYNGEAL POUCH the third arch Epithelium of the dorsal region forms the superior parathyroid gland D. FOURTH BRACHIAL ARCH Ventral region gives rise to the ultimobranchial body Cartilage Cells of the ultimobranchial body gives rise to the parafollicular o Thyroid Cartilage cells, or C cells, of the thyroid gland. These cells secrete Muscular Component calcitonin, a hormone involved in the regulation of the calcium o 3 pharyngeal constrictors, cricothyroid muscle level in the blood. Levator veli palatini Aortic Arch o Left-aortic arch o Right- right subclavian Nerve o Superior laryngeal branch of Vagus (CN X), the nerve of the fourth arch E. SIXTH BRACHIAL ARCH Cartilage Table 2. Derivatives of the Pharyngeal Pouches. o Cricoid, arytenoid, corniculate, cuneiform Muscular Component II. DEVELOPMENT OF THE FACE o Intrinsic muscles of larynx Aortic arch Five facial primordia appear as prominences around o Left-pulmonary artery, ductus arteriosus the stomodeum: o Right-pulmonary artery, distal end degenerates o The single frontonasal prominence Nerve o The paired maxillary prominences o Recurrent laryngeal nerve of Vagus (CN X), the o The paired mandibular prominences nerve of the sixth arch By the end of the fourth week, all five swellings have appeared. PHARYNGEAL POUCHES The maxillary swellings can be distinguished lateral, and The human embryo has four pairs of pharyngeal pouches; the the mandibular swellings caudal to the stomodeum fifth is rudimentary The paired maxillary swellings enlarge and grow Because the epithelial endodermal lining of each pouches ventrally and medially. gives rise to a number of important organs, the fate of each A pair of ectodermal thickenings called the nasal pouch is discussed separately. placodes appear on the frontonasal process and begin to FIRST PHARYNGEAL POUCH enlarge Forms a stalk-like diverticulum, the tubotympanic recess, During the fifth week, the ectoderm at the center of each which comes contact with the epithelial lining of the first nasal placode invaginates to form an oral nasal pit, pharyngeal cleft. Page 3 of 17 CMED 1D  (007) EMBRYONIC DEVELOPMENT OF THE HEAD, NECK, EYES, AND EARS DR. C. PANO | 01/25/21 dividing the raised rim of a placode into a lateral nasal Anteriorly, secondary palate fuses with primary palate process and a medial nasal process. Incisive foramen is midline mark of fusion of primary Each medial nasal process begins to migrate towards and secondary palate other and they fuse. The mandibular swellings have now fused to create the A. DEVELOPMENT OF HARD AND SOFT primordial lower lip. The nasal pits deepen and fuse to form a single, PALATE enlarged, ectodermal nasal sac. Ossification provides basis for bony Hard palate lateral and inferior expansion of each fused medial Ossification of palate starts at 8th week by 1 ossification nasal process forms the intermaxillary process. center The tips of the maxillary swellings grow to meet this Posterior 1/3rd remain unossified, mesenchyme migrates process and fuse with it. into this region from 1St and 4th pharyngeal arch to The intermaxillary process gives rise to the bridge and provide the soft palate muscles septum of the nose, and the philtrum on the upper lip. Fusion of primary and secondary palate occur at 1St ectoderm and mesoderm of frontal process and each Post-natal year medial nasal process proliferate, forming a midline nasal septum. V. DEVELOPMENT OF JAWS This divides the nasal cavity into two nasal passages which open into the pharynx, behind the secondary Maxillary prominence grows medially, compressing palate, through the definitive choana. medial nasal prominences toward midline The philtrum is now formed, and the lateral portions of the Subsequently cleft between them is lost to form upper lip maxillary and mandibular swellings fuse to create the and jaw cheeks and reduce the mouth to its final width. Lower lip and jaw forms from the mandibular prominences that merge across the midline PROMINECE STRUCTURES FORMED Frontanasal* Forehead, bridge of nose, and medial VI. DEVELOPMENT OF MANDIBLE and lateral nasal prominences Maxillary Cheeks, lateral portion of upper lip A. PRENATAL DEVELOPMENT OF MANADIBLE Medial nasal Philtrum of upper lip, crest, and tip of Both intramembranous and cartilaginous type nose Body and ramus are derived from intramembranous Lateral nasal Alae of nose ossification Mandibular Lower lip Coronoid process, condylar process and mental Table 3. Structures Contributing to Formation of the Face. process develop from cartilage III. DEVELOPMENT OF PARANASAL B. POSTNATAL DEVELOPMENT OF MANDIBLE SINUSES Main site for post-natal growth of mandible is condylar cartilage They develop as diverticulae of the walls of the nasal It grows in upward and backward direction thereby cavity. displacing mandible in downward and forward direction Maxillary sinuses and few anterior & posterior ethmoidal Remodeling at ramus and alveolar ridges is air cells develop in fetal life. responsible for increase in height, width and length Frontal and sphenoidal sinuses develop after birth. Enlargement of maxillary sinus is by resorption at VII. DEVELOPMENT OF MAXILLA internal walls except medial wall IV. DEVELOPMENT OF PALATE A. PRENATAL DEVELOPMENT OF MAXILLA Intramembranous development maxillary prominences known as palatine shelves Maxilla is divided into various skeletal units Initially the palatine shelves are directed obliquely Growth of each unit is influenced by associated downward on either side of tongue functional matrix At 7th week, palatine shelves ascend to attain a o Body-infraorbital nerve horizontal position above the tongue and fuse to form o Orbital unit-eyeball secondary palate o Nasal unit-septal cartilage Page 4 of 17 CMED 1D  (007) EMBRYONIC DEVELOPMENT OF THE HEAD, NECK, EYES, AND EARS DR. C. PANO | 01/25/21 o Alveolar unit-teeth The site of union between the base and body of the tongue is Note- single ossification centre for each maxilla delineated by a V-shaped groove called sulcus terminalis. Displacement The occipital myotomes migrate anteriorly into the o Due to formation of bone at cranial base tongue during the 5th to 7th weeks. o Moves the maxilla in downward and forward Later, various types of papillae differentiate in the dorsal direction mucosa of the body of the tongue, whereas lymphatic tissue Remodelling develop into the base of the tongue o Deposition at anterior surface and resorption at posterior surface moves the maxilla in forward IX. DEVELOPMENT OF TONGUE direction Depositon at palatal surface and resorption at nasal surface Appears in embryos of approximately 4 weeks in the form of moves it downward two lateral lingual swellings and one medial swelling, the tuberculum impar B. FORMATION OF PREMAXILLA o These three swellings originate from the first Fusion maxillary prominence with 2 medial nasal pharyngeal arch. prominences is at surface as well as deeper levels which The tongue is composed of the body which is the movable oral forms intermaxillary segments part and the posterior (attached) base or pharyngeal part. Intermaxillary segment is composed of The tongue develops from the tissues of the 1St, 2nd and 3rd o Labial component- form philtrum of the upper lip branchial arches and from the occipital myotomes. o Upper jaw component- carries the four incisal The body of the tongue develops from 3 elevations on the region of upper jaw ventromedial aspect of the 1ST arch: a tuberculum impar and Palatal component- forms the primary palate paired lateral lingual swellings. These lateral lingual swellings rapidly enlarge, merge with each other, and overgrow the VIII. DEVELOPMENT OF TMJ tuberculum impar to form the oral part of the tongue. A U-shaped sulcus develops in front and on both sides of this Early TMJ develops from the first branchial arch mesenchyme oral part, which allows it to be free and highly mobile except and is therefore innervated by fifth cranial nerve. This is the at the region of the frenum lingulae. early embryonic joint. This early embryonic joint is the joint between malleus and A. INNERVATIONS OF THE TONGUE incus which develops from first branchial arch. As the occipital muscle masses migrate anteriorly, the This joint serves as the primary TMJ joint up to 16 weeks of 9th and 12th nerves are carried along into the tongue. prenatal life. This joint is an uniaxial hinge joint capable of no The 5th nerve supplies sensory fibres to the body or anterior lateral motion. 2/3rds of the tongue. By the end of 7-11 weeks of gestation, the secondary The 7th nerve supplies the taste fibres to the same TMJ begins to develop part. i.e., At about 9th week – a condensation of mesenchyme The 9th nerve supplies sensory taste fibres to the appears surrounding the upper posterior surface of posterior 1/3rd of the tongue. rudimentary ramus (joint capsule develops from the The hypoglossal nerve supplies the intrinsic muscles condensed mesenchyme) (longitudinal, vertical and transverse) and the extrinsic At about 12 th week of IUL,2 clefts appear in that muscles (styloglossus, hyoglossus and genioglossus). mesenchyme - producing the upper and lower joint cavities The remaining intervening mesenchyme – becomes the intra X. DEVELOPMENT OF THYROID GLAND articular disc. (Which will be well defined by 16th week of IUL) At birth – mandibular fossa (in temporal bone) is flat, without Appears as an epithelial proliferation in the floor of the any articular eminence, this becomes prominent only after the pharynx between the tuberculum impar and the copula at eruption of deciduous dentition. a point later indicated by the foramen cecum The base of the tongue develops mainly from the 3rd The thyroid descends in front of the pharyngeal gut as a branchial arch. Initially, it is indicated by 2 midline elevations bilobed diverticulum. During this migration, the thyroid that appear caudal to the tuberculum impar. remains connected to the tongue by a narrow canal, the These are the copula of the 2nd arches and the large thyroglossal duct. hypobranchial eminence of the 3rd and 4th arches. It reaches its final position in front of the trachea in the Later the hypobranchial eminence overgrows the 2nd seventh week branchial arches to become continuous with the body of the tongue. Page 5 of 17 CMED 1D  (007) EMBRYONIC DEVELOPMENT OF THE HEAD, NECK, EYES, AND EARS DR. C. PANO | 01/25/21 Begins to function at approximately the end of the third Mesenchymal cells on the outside of the tooth and in month contact with dentin of the root differentiate into Follicular cells produce the colloid that serves as a source cementoblasts. of thyroxine and triiodothyronine. periodontal ligament Parafollicular cells, or C cells, derived from the - derived from mesenchyme outside of the cement layer ultimobranchial body serve as a source of calcitonin. - holds the tooth firmly in position and functions as a shock absorber XI. DEVELOPMENT OF TEETH With further lengthening of the root, the crown is gradually pushed through the overlying tissue layers into the oral cavity. arise from an epithelial-mesenchymal interaction between overlying oral epithelium and underlying The eruption of deciduous or milk teeth occurs mesenchyme derived from neural crest. 6 to 24 months after birth. 6th week of development, the basal layer of the During the third month of development, buds for the epithelial lining of the oral cavity forms a C-shaped permanent teeth, which lie on the lingual aspect of the structure, the dental lamina. milk teeth are formed. This lamina, gives rise to a number of dental buds in each jaw, which form the primordia of the ectodermal components of the teeth. Soon, the deep surface of the buds invaginates, resulting in the cap stage of tooth development, which consists of: - outer dental epithelium- outer layer - inner dental epithelium- inner layer - stellate reticulum- central core of loosely woven tissue The mesenchyme, which originates in the neural crest in the indentation, forms the dental papilla. Mesenchyme cells of the papilla adjacent to the inner Figure 2. Formation of the tooth at successive stages of dental layer differentiate into odontoblasts, which later development. A. Bud stage (8 weeks), B. Cap Stage (10 weeks), produce dentin. C. Bell stage (3 months), D. 6 months. With thickening of the dentin layer, odontoblasts retreat into the dental papilla, leaving a thin cytoplasmic process These buds remain dormant until approximately the sixth (dental process) behind in the dentin year of postnatal life. Then they begin to grow, pushing The odontoblast layer persists throughout the life of the against the underside of the milk teeth and aiding in the tooth and continuously provides predentin. The shedding of them. remaining cells of the dental papilla form the pulp of the As a permanent tooth grows, the root of the overlying tooth. deciduous tooth is resorbed by osteoclasts. In the meantime, epithelial cells of the inner dental epithelium differentiate into ameloblasts (enamel formers). These cells produce long enamel prisms that A. MOLECULAR REGULATION OF TOOTH are deposited over the dentin. DEVELOPMENT enamel knot- regulates early tooth development Teeth are present only in vertebrates and parallel -formed by a cluster of cells in the inner dental the evolutionary appearance of the neural crest. epithelium Regulation of tooth patterning from incisors to -first laid down at the apex of the tooth and from here molars is generated by a combinatorial expression spreads toward the neck of HOXgenes expressed in the mesenchyme. -When the enamel thickens, the ameloblasts retreat into Signals for development involve growth factors including the stellate reticulum. WNTs, BMPs, and FGFs; the secreted factor SHH; and Formation of the root of the tooth begins when the dental transcription factors, such as MSXl and MSX2, that epithelial layers penetrate into the underlying interact in a complex pathway to produce cell mesenchyme and form the epithelial root sheath. differentiation and patterning for each tooth. As more and more dentin is deposited, the pulp chamber enamel knot narrows and finally forms a canal containing blood -‘’organizer” for tooth development vessels and nerves of the tooth. Page 6 of 17 CMED 1D  (007) EMBRYONIC DEVELOPMENT OF THE HEAD, NECK, EYES, AND EARS DR. C. PANO | 01/25/21 -appears in a circumscribed region of the dental C. THIRD ARCH ANOMALIES epithelium at the tips of the tooth buds. Hyoid anomalies -it enlarges at the cap stage into a tightly packed group o Lower body of cells but undergoes apoptosis and disappears by the o Greater horn end of this stage. Aneurysm of carotid artery XII. CLINICAL CORRELATIONS D. FOURTH ARCH ANOMALIES Laryngeal stenosis A. FIRST ARCH ANOMALIES Laryngoptosis (low position of larynx) Involves malformations of eyes, ears, palate, and mandible Chondromalacia Two main manifestation of “First arch Syndrome” Double aortic arch 1. TREACHER COLLINS SYNDROME Pulmonary artery sling - Mandibulofacial dysostosis o Left pulmonary artery originates from right - Inherited AD (AUTOSOMAL DOMINANT) pulmonary artery - Occurring in 1/50,000 live births with 60% of o Slings around right main-stem bronchus cases arising as new mutations. - Features E. FIRST POUCH ANOMALIES a. Midface maxilla, zygomatic arches and mandibular hypoplasia Atretic eustachian tube → recurrent OM b. ear anomalies: microtia, anotia, stenotic or ET diverticuli atresia of EAC, malformation of malleus Absence and incus (CHL) o Tympanic cavity c. Eye anomalies: coloboma of lower lids, o Mastoid antrum down- slopping palpebral fissures Perforated TM d. Cleft palate Bifid tongue - Mutations in the TCOF1 gene [5q32] are responsible Branchiogenic nasopharyngeal cysts (very rare) for most cases. - Treacle: product of TCOF1 gene that appears to be F. SECOND POUCH ANOMALIES necessary for preventing apoptosis and maintaining THYROGLOSSAL DUCT CYST proliferation in neural crest cells but not for regulating o 7% of population their migration o May lie at any point along the migratory pathway - Phenocopies can be produced in laboratory animals of the thyroid gland but is always near or in the following exposure to teratogenic doses of retinoic midline of the neck. acid o Failure of ablation of TGD 2. PIERRE ROBIN SYNDROME o Anywhere from base of tongue to upper - May be due to genetic or environmental factors mediastinum - Occurs in approximately1/8,500 births. o Typical finding - 3 Main features ▪ Cystic lesion just below hyoid in a. Micrognathia (small mandible) midline that moves with deglutination b. Glossoptosis (posterior and tongue protrusion displacement/retraction of tongue) o May contain thyroid tissue c. Cleft palate (U-shaped) ▪ Potentially the only functioning thyroid o Perform U/S or CT to look for thyroid and to B. SECOND ARCH ANOMALIES assess lesion Malformed auricle o Treatment – surgical o Microtia o may contain cancer-1% Papillary carcinoma Ossicular malformation LINGUAL THYROID o Stapes, malleus, incus o Failure of decent of thyroid -> atopic o CHL ▪ 90% of cases at the base of tongue Muscular asymmetry of face (lingual thyroid) Hyoid malformation o 4:1 female:male o Lesser horn and upper body o Usually not noted until teenage or young adult Page 7 of 17 CMED 1D  (007) EMBRYONIC DEVELOPMENT OF THE HEAD, NECK, EYES, AND EARS DR. C. PANO | 01/25/21 o Asymptomatic (most cases); dysphagia, airway thymic hypoplasia or aplasia that disrupts the compromise immune system’s T cell—mediated response. o Reddish mass (well vascularized) at base of HEMIFACIAL MICROSOMIA tongue o Oculoauriculovertebral spectrum or Goldenhar o Hypothyroidism – 70% of cases syndrome o 2/3 cases – only functioning thyroid tissue o Craniofacial abnormalities that involve the maxillary, ▪ Thyroid function study prior to temporal, and zygomatic bones treatment o Ear (anotia, microtia), eye (tumors and dermoids in o Treatment the eyeball), and vertebral (fused and ▪ Asymptomatic – Monitor hemivertebrae, spina bifida]) defects are commonly ▪ Symptomatic observed in these patients. Excise +/- transplant tissue into muscles of neck J. ANKYLOGLOSSIA (TONGUE TIE) Radioiodine therapy The tongue is not freed from the floor of the mouth. (destroys all thyroid tissue) Normally, extensive cell degeneration occurs, and the ▪ Usually require lifelong thyroid frenulum is the only tissue that anchors the tongue to the replacement floor of the mouth. In the most common form of ankyloglossia, the frenulum extends to the tip of the G. THIRD AND FOURTH POUCH ANOMALIES tongue. DIGEORGE SYNDROME o Congenital absence of thymus and parathyroids K. TOOTH ABNOMALITIES o Partial deletion of chromosome 22 NATAL TEETH o CATCH -22 - have erupted by the time of birth Cardiac anomalies -usually involves the mandibular incisors, which may be Abnormal facies abnormally formed and have little enamel Thymic aplasia TETRACYCLINES Cleft palate - discoloration of teeth due to foreign substances Hypocalcemia DEFICIENT IN ENAMEL o Tetany and impaired cellular immunity (T-cells) - caused by vitamin D deficiency (rickets) H. DEVELOPMENTAL DEFECTS OF SALIVARY L. FACIAL DEFECTS GLANDS Cleft lip and cleft palate are common defects that result Agenesis in abnormal facial appearance and difficulties with Aplasia speech. Atresia of ducts The incisive foramen is considered the dividing Xerostomia landmark between anterior and posterior cleft Developmental lingual salivary gland depression deformities. Anterior lingual depression Those anterior to the incisive foramen include lateral cleft lip, cleft upper jaw, and cleft between the primary and secondary palates. I. NEURAL CREST CELLS AND Such defects are due to partial or complete lack of fusion CRANIOFACIAL DEFECTS of the maxillary prominence with the medial nasal TREACHER COLLINS prominence on one or both sides. ROBIN SEQUENCE Those that lie posterior to the incisive foramen include 22Q11.2 DELETION SYNDROME cleft (secondary) palate and cleft uvula. o DiGeorge syndrome, DiGeorge anomaly, Cleft palate results from a lack of fusion of the palatine velocardiofacial syndrome, Shprintzen, syndrome, shelves, which may be due to: conotruncal anomaly face syndrome, and congenital - smallness of the shelves thymic aplasia and hypoplasia -failure of the shelves to elevate o Infants most often present with congenital heart and -inhibition of the fusion process itself aortic arch defects, mild facial dysmorphology, -failure of the tongue to drop from between learning disabilities, and frequent infections due to the shelves because of micrognathia Page 8 of 17 CMED 1D  (007) EMBRYONIC DEVELOPMENT OF THE HEAD, NECK, EYES, AND EARS DR. C. PANO | 01/25/21 Van der Woude syndrome- most common syndrome ▪ the internal ear, which converts sound waves into associated with cleft lip with or without cleft palate. nerve impulses and registers changes in -inherited as an autosomal dominant and is due equilibrium. to mutations in INTERFERON REGULATORY FACTOR 6 [IRF6; 1p32—41] that is expressed A. INTERNAL EAR in the medial [fusing] edge of the palatal 1. OTIC PLACODES shelves. Day 22 - 88% of affected infants will have pits in Thickening of surface ectoderm on each side of their lower lip, and in 64% of these individuals, rhombencephalon this will be the only abnormality. These thickening, the otic placodes, invaginate Oblique facial clefts-produced by failure of the rapidly to form the otic or auditory vesicles maxillary prominence to merge with (OTOCYST) its corresponding lateral nasal prominence along the line of the nasolacrimal groove - when this occurs, the nasolacrimal duct is usually exposed to the surface Median [midline] cleft lip- a rare abnormality; caused by incomplete merging of the two medial nasal prominences in the midline. -Infants with midline clefts are often cognitively Figure 4. A. An embryo at the end of the fourth week of impaired and may have brain abnormalities development showing the otic and optic vesicles. B. Region of the that include varying degrees of loss of midline Rhombencephalon showing the otic placodes in a 22-day embryo. structures. Loss of midline tissue may be so extensive that the lateral ventricles fuse [holoprosencephaly] 2. OTOCYST - These defects are induced very early in Otic or auditory vesicles development, at the beginning of neurulation Cells from the otocyst differentiate to form [days 19 to 21] when the midline of the forebrain ganglion cells for vestibulocochlear ganglia is being established. During later development, each vesicle divides into: Membranous labyrinth o Ventral – saccule and cochlear duct o Dorsal – utricle, semicircular canal, endolymphatic duct. Figure 3. Different Facial Cleft. A. Bilateral Cleft, B. Cleft Palate, C. Oblique Facial Cleft, D. Midline Cleft Lip. Figure 5. A,B. Development of the otocyst showing a dorsal XIII. EAR utricular portion with the endolymphatic duct and a ventral saccular portion. C-E. Cochlear duct at 6, 7, and 8 weeks, respectively. Adult = forms one anatomic unit: hearing and equilibrium Note formation of the ductus reuniens and the utriculosaccular In the embryo, it develops from three distinctly different duct. parts: ▪ the external ear, the sound-collecting organ; 3. SUBCOCHLEAR DUCT ▪ the middle ear, a sound conductor from the 6th week of development external to the internal ear; and Page 9 of 17 CMED 1D  (007) EMBRYONIC DEVELOPMENT OF THE HEAD, NECK, EYES, AND EARS DR. C. PANO | 01/25/21 Tubular outpocketing at the lower pole of the o Bascular membrane: scala tympani saccule o Lateral wall will remain attached to the Penetrates the surrounding mesenchyme until surrounding cartilage by the spiral ligament the end of the eighth week o Median angle is supported by long cartilaginous 4. SPIRAL ORGAN OF CORTI process the modiolus which will further develop 7th week into bony cochlea. Derived from cells of the cochlear duct Initially the epithelial cells of the cochlear duct are Transduces sound vibrations into electrical alike. signals for hearing With further development, however, they form two ridges: Sensory cells and tectorial membrane o Inner ridge: spiral limbus Impulses are transmitted to the spiral ganglion o Outer ridge form and then to the nervous system by the auditory ▪ Hair cells fibers of CN V III o Inner, 3 or 4 outer o Sensory cells of the auditory system DUCTUS REUNIENS o They are covered by Tectorial membrane, a o connection between the cochlear duct fibrillar gelatinous substance attached to the and the remaining portion of the spiral limbus that rests with its tip on the hair saccule cells. 6. SEMICIRCULAR CANALS 6th week Flattened outpocketings of the utricular part of the otic vesicle Central appose each other and disappear, giving rise to the three semicircular canals o Crus ampullare o Crus nonampullare does not widen. Because two of the latter type fuse, however, only five crura enter the Figure 6. Development of the Organ of Corti. A. 10 weeks, B. utricle, three with an ampula and two Approx. 5 months, C. Full-term infant. without. Cells in the ampullae form a crest, Crista 5. 10TH WEEK OF DEVEELOPMENT ampullaris Contain sensory cells for Mesenchyme differentiates into cartilage maintenance of equilibrium Cartilaginous shell undergoes vacuolization Maculae acusticae Form Two perilymphatic spaces: o Develop in the walls of the utricle and o Scala vestibule saccul o Scala tympani Impulses from cristae and maculae o Result of a change in position of the body o Innervated by the Vestibular fibers of CN VIII. Statoacoustic ganglion o small group of cells that breaks away from otic vesicle Other cells derived from neural crest. The ganglion subsequently splits into the following: o Cochlear Supply sensory cells of the Figure 7. Development of the scala tympani and scala vestibuli. Organ of Corti o Vestibular ▪ The cochlear duct is then divided or separated from Supply the saccule, utricle, o Vestibular membrane: scala vestibule and semicircular canals Page 10 of 17 CMED 1D  (007) EMBRYONIC DEVELOPMENT OF THE HEAD, NECK, EYES, AND EARS DR. C. PANO | 01/25/21 TYMPANIC ANTRUM o Late fetal life o Tympanic cavity expands dorsally by vacuolization of surrounding tissue o After birth, the epithelium of the tympanic cavity invades the bone of the developing mastoid process, and epithelium-lined air sacs are formed (Pneumatization). o Expansion of inflammations of the Figure 8. Development of the semicircular canals. middle ear into the antrum and mastoid air cells is a common complication of B. MIDDLE EAR the middle ear infections 1. TYMPANIC CAVITY Originates in the endoderm C. EXTERNAL EAR Derived from the first pharyngeal pouch 1. EXTERNAL AUDITORY MEATUS o Lateral: floor of the first pharyngeal Develops as an invagination of first arch tissue cleft and not from the first pharyngeal cleft as o Distal: the tubotympanic recess - previously believed. primitive tympanic cavity At the beginning of the 3rd month – epithelial cells o Proximal: auditory tube (eustachian at the bottom of the meatus proliferate, forming a tube) – will be the communication solid plate, the meatal plug between the tympanic cavity and the 7th month- this will dissolve in the epithelium lining nasopharynx of the floor of the meatus form the eardrum Congenital Deafness - meatal plug persists until birth that will result into congenital deafness. Figure 9. A. Derivatives of the first three pharyngeal arches. The malleus and incus form at the dorsal tip of the first arch and the stapes at that of the second arch. B. Middle ear showing the handle of the malleus in contact with the eardrum. Figure 10. Ear showing the external auditory meatus, the middle ear with its ossicles, and the inner ear. 2. OSSICLES First pharyngeal arch: malleus and incus 2. EARDRUM OF THE TYMPANIC MEMBRANE Second pharyngeal arch: stapes Made up of: Although the ossicles appear during the first half a. An ectodermal epithelial lining at the of fetal life, they remain embedded in bottom of the auditory meatus mesenchyme until 8th month. b. An endodermal epithelial lining of the MALLEUS tympanic cavity o Tensor tympani c. An intermediate layer of connective ▪ Innervation: CNV mandibular tissue: fibrous stratum. branch Major: firmly attached to the handle of the malleus STAPES Remaining portion: forms the separation between o Stapedius muscle the external auditory meatus and tympanic cavity. ▪ Innervation: CN VII Facial 3. AURICLE Nerve Page 11 of 17 CMED 1D  (007) EMBRYONIC DEVELOPMENT OF THE HEAD, NECK, EYES, AND EARS DR. C. PANO | 01/25/21 ▪ From six mesenchymal proliferations at the dorsal Unique origin: Footplate is derived from neural crest cells end of the first and second pharyngeal arches, and paraxial mesoderm surrounding the first pharyngeal cleft Stapes fixation (ankylosis) – most common defects ▪ Auricular hillocks a. 3 on each side of the external meatus b. Fuse and form the definitive auricle C. EXTERNAL EAR DEFECTS c. Derived from neural crest cells External ear is derived from neural crest cells Neural crest cells contribute to development of many XIV. HEARING structures Dependent on sound waves that cause vibrations in the TM, which is held tightly like the surface of a drum by the Serves as a clue to Examine infants for other tensor tympani muscle. abnormalities! Too loud: tensor tympani + stapedius muscle stretches All the frequently occurring chromosomal the membrane syndromes and most of the less common ones have TM vibration ear anomalies as one of their characteristics. o Movement of ossicles to amplify the force of the sound wave and to transmit the pressure of the D. PREAURICULAR APPENDAGES AND PITS wave to the cochlea through the oval window Skin tags and shallow depression anterior to the ear Amplification Pits arise when invagination of first arch tissues to form Large size difference bet TM (55 mm2) and oval the external auditory meatus fails to occur properly. window (3.2 mm2) Indicate abnormal development of auricular hillocks Shape o Malleus - acts like a lever to increase Appendages can occur when misexpression of genes regulating development of the external ears results in the force received by the stapes duplications of tissue growth and differentiation Pressure produced by movement of the stapes at the oval window creates a fluid wave in the cochlea that is balanced by movement of the round window. The fluid XV. EYE wave moves small regions of the basilar membrane and the location of these regions is determined in part by the amplitude (loudness) and frequency (pitch) of the wave High frequencies (high pitch) are heard near the oval window where fibers connecting the basilar membrane are shorter and stiffer A. CLINICAL CORRELATION 1. HEARING LOSS AND EXTERNAL EAR ABNORMALITIES Congenital hearing loss o Abnormaliities of the hair cells or Figure 11. Embryo at the end of 4 weeks of development showing auditory nerve ganglia (sensorineural) the otic and optic vesicles. o Structutal defects in external ear canal, eardrum or ossicles (conductive) o 50% genetic: AD or AR or X-Linked A. OPTIC CUP AND LENS VESICLE 2. RISK FACTORS Day 22 Treacher Collins Syndrome Pair of shallow grooves on the sides of the forebrain Down Sydrome Optic vesicles Prenatal Infections o Outpocketing of forebrain Maternal DM o From closure of the neural tube Retinoid o Surface ectoderm: Lens formation 1. OPTIC CUP B. STAPES From invagination of optic vesicles Most common ossicle involved in conductive hearing Intraretinal space Page 12 of 17 CMED 1D  (007) EMBRYONIC DEVELOPMENT OF THE HEAD, NECK, EYES, AND EARS DR. C. PANO | 01/25/21 o Separates inner and outer layers ▪ Rods are more numerous (120 million) initially and more sensitive than cones (6 to 7 o Disappears, and the two layers appose ▪ million) but do not detect color like the each other cones. Choroid fissure Mantle layer o Invagination of inferior surface of optic o Gives rise to neurons and supporting cells cup ▪ Outer nuclear layer o Hyaloid artery: Inner chamber of the ▪ Inner nuclear layer eye ▪ Ganglion cell layer o 7th week AOG Fibrous layer ▪ Fusion of choroid fissure o Contains axons of nerve cells of the deep layers ▪ Mouth of optic cup becomes o Converge toward the optic stalk → optic nerve a round opening of the future pupil. Pars ceca retinae o Anterior fifth of the inner layer o Divides into: ▪ Pars indica retinae (inner layer of the iris) ▪ Pars ciliaris retinae (ciliary body) Figure 12. A. Ventrolateral view of the optic cup and optic stalk of a 6-week embryo. 2. LENS VESICLE Form closure of choroid fissure 5th week AOG Loses contact with the surface ectoderm and lies in the mouth of the optic cup Figure 14. Various layers of the pars optica retinae in a fetus of approximately 25 weeks. C. IRIS Between the optic cup and the overlying surface epithelium is filled with loose mesenchyme Sphincter and dilator pupillae muscles form Muscles develop from ectoderm of the optic cup Figure 13. Section through the eye of a 7-week embryo. Adult o Pigment - containing external layer B. RETINA o Unpigmented internal layer of the optic cup Outer layer of the optic cup o Layer of richly vascularized connective tissue o Pigmented layer that contains the pupillary muscles Inner layer o Pars óptica retina D. CILIARY BODY ▪ Posterior ⅘ Pars ciliaris retinae ▪ Cells bordering the intraretinal space o Easily recognized by its marked folding ▪ Differentiate into Externally ▪ Rods (120 million) o Forms the ciliary muscle ▪ Cones (6 to 7 million) Internally Page 13 of 17 CMED 1D  (007) EMBRYONIC DEVELOPMENT OF THE HEAD, NECK, EYES, AND EARS DR. C. PANO | 01/25/21 o Connected to the lens by Zonula or Suspensory G. ANTERIOR CHAMBER Ligament Forms through vacuolization Contraction of the ciliary muscle changes tension in the Splits into: ligament and controls curvature of the lens. o Inner: in front of the lens and iris, the iridopupillary membrane o Outer: continuous with the sclera, the substantia propria of the cornea Lined by flattened mesenchymal cells. H. CORNEA Formed by: 1. Epithelial layer from the surface ectoderm Figure 15. Development of the iris and ciliary body. 2. Substantia propria or stroma, continuous with sclera E. LENS 3. Epithelial layer, borders the anterior chamber After formation of the lens vesicle Iridopupillary membrane disappears completely o Cells of the posterior wall begin to elongate anteriorly and form long fibers that gradually fill I. POSTERIOR CHAMBER the lumen of the vesicle Space between iris anteriorly and the lens and ciliary body 7th week AOG posteriorly o Primary lens fiber reach anterior o Secondary lens fibers = central J. PUPIL Communication between anterior and posterior F. CHOROID, SCLERA, AND CORNEA chambers 5th week AOG Aqueous Humor o Completely surrounded by loose mesenchyme o Fluid produced by the ciliary process of the o Differentiates into: ciliary body ▪ Inner layer: Pia mater o Circulates from the posterior chamber into the - Choroid anterior chamber ▪ Outer layer: Dura mater o Providing nutrients for the avascular cornea and - Sclera lens - Continuous with dura mater o Anterior chamber → Canal of the Schlemm of optic nerve (Scleral venous sinus) → Iridocorneal angle → Resorbed into the bloodstream Glaucoma o Blockage of the flow of fluid at the canal of Schlemm K. VITREOUS BODY Mesenchyme invades inside of the optic cup thru choroid fissure Hyaloid vessels o Intrauterine life supply o Supply the lens and forms the vascular layer of the inner surface of the retina Figure 16. Section through the eye of a 15-week fetus showing o The interstitial spaces of this network later fill the anterior chamber, iridopupillary membrane, inner and outer with a transparent gelatinous substance forming vascular layers, choroid and sclera. the vitreous body o Obliterated and disappear during fetal life, leaving behind the hyaloid canal Page 14 of 17 CMED 1D  (007) EMBRYONIC DEVELOPMENT OF THE HEAD, NECK, EYES, AND EARS DR. C. PANO | 01/25/21 Initially, expressed in a band in the anterior L. OPTIC NERVE neural ridge of the neural plate before neurulation begins Optic cup is connected to the brain by the optic stalk, At this stage, there is a Single eye field → which has a groove, the choroid fissure, on its ventral separates into two optic primordia surface 1. SHH In this groove are the hyaloid vessels. The nerve fibers of Signal for separation of this field is SONIC the retina returning to the brain lie among the cells of the HEDGEHOG (SHH) expressed in the inner wall of the stalk prechordal plate. 7th week AOG SHH expressions upregulates PAX2 in the o Choroid fissure closes, forms a tunnel inside center of the eye field and downregulates PAX6 optic stalk Later, this pattern is maintained that PAX2 ▪ As a result of the continuously expressed in optic stalk and PAX6 is increasing number of nerve fibers, the expressed in the optic cup and overlying inner wall of the stalk grows, and the surface endoderm that forms the lens inside and outside walls of the stalk Optic cup formation fuse a. As development proceeds, it appears ▪ Cells of the inner layer provide a that PAX6 is not essential for optic cup network of neuroglia that supports the formation. Instead, this process is optic nerve fibers regulated between optic vesicle and o Optic stalk transformed into the optic nerve mesenchyme and the overlying Center: hyaloid artery → later called central retinal artery surface ectoderm in the lens-forming Outside: continuation of the choroid and sclera → the pia region arachnoid and dura layer of the nerve, respectively, Fibroblast growth factors (FGFs) surround the optic nerve a. Promote differentiation of the neural (inner layer) retina Transforming growth factor β (TGF - β) a. Secreted by surrounding mesenchyme, directs formation of the pigmented (outer) retinal layer Lens ectoderm a. Essential for proper formation of the Figure 17. Transformation of the optic stalk into the optic nerve. optic cup, such that without a lens placode, no cup invagination occurs M. MOLECULAR REGULATION OF EYE Differentiation of the lens depends on PAX6, although the genes is not responsible for DEVELOPMENT inductive activity by the optic vesicle. Instead, PAX6 acts in the surface ectoderm to regulate lens development. N. CLINICAL CORRELATION 1. COLOBOMA Failure of closure of the choroid fissure, normally this fissure closes during the seventh week of development When it does not, a cleft persists. Although such a cleft is usually in the iris only – coloboma Figure 18. The regulation factor involved in eye development. iridis. Can extend to the ciliary body, retina, choroid, 1. PAX6 optic nerve, eyelids Key regulatory gene for eye development Coloboma is a common eye abnormality Member of the PAX (paired box) family of frequently associated with other eye defects transcription factors Page 15 of 17 CMED 1D  (007) EMBRYONIC DEVELOPMENT OF THE HEAD, NECK, EYES, AND EARS DR. C. PANO | 01/25/21 PAX2 gene mutation. Renal defects also occur with mutations in PAX2 as part of the renal coloboma syndrome. Figure 22. Anophthalmia. Figure 19. Coloboma iris. 5. CONGENITAL APHAKITA AND ANIRIDIA 2. CONGENITAL CATARACT Absence of the lens Lens opacity during intrauterine life Absence of iris Risk factors: Rare o German measles during 4th-7th week AOG Result from disturbances in induction and o Associated with hearing loss development of tissues Because of the MMR (measles, mumps, and PAX6 mutation result in aniridia and may rubella) vaccine, congenital rubella contribute to syndrome has been nearly eradicated in the US. Figure 23. Patient with aniridia (absence of the iris). 6. CYCLOPIA Single eye and synophthalmia (fusion of the eyes) Comprise a spectrum of defects in which the Figure 20. Congenital Cataract. eyes are partially or completely fused Loss of midline tissue that may occur as early 3. MICROPHThALMIA as days 19 to 21 of gestation or at later stages Eye is too small; Eye occupied ⅔ of its volume when facial development is initiated. Usually associated with other ocular This loss results in the underdevelopment of abnormalities the forebrain and frontonasal prominence. Risk factors: o Intrauterine infections: CMV, Toxoplasmosis Figure 21. Microphthalmia. 4. ANOPHTHALMIA Figure 24. Synophtalmia. Absence of the eye In some histological analysis reveals some ocular tissue. Accompanied by severe cranial abnormalities. Page 16 of 17 CMED 1D  (007) EMBRYONIC DEVELOPMENT OF THE HEAD, NECK, EYES, AND EARS DR. C. PANO | 01/25/21 TEST YOUR KNOWLEDGE C. an intermediate layer of connective tissue that forms the fibrous stratum 9. The intermaxillary segment forms via the fusion of the A. 1. Mandibulofacial dysostosis (Treacher-Collins syndrome) is a developmental disorder characterized by craniofacial maxillary prominences deformities, including malformed or absent ears, A. mandibular prominences zygomatic and mandibular hypoplasia, and downward B. palatine shelves slanting eyes exhibiting ptosis of the lateral eyelids. This C. lateral nasal prominences condition is the result of lack of migration of neural crest D. medial nasal prominences 10. Congenital absence of thymus and parathyroids cells into what pharyngeal arch? A. First pharyngeal arch A. Ankyloglossia B. Second pharyngeal arch B. Pierre Robin Syndrome C. Third pharyngeal arch C. Thyroglossal duct cyst D. Fourth pharyngeal arch D. DiGeorge Syndrome E. Fifth pharyngeal arch E. Treacher Collins Syndrome 2. The most common site of a thyroglossal cyst is A. dorsal aspect of the neck REFERENCE B. anterior border of the sternocleidomastoid Sadler, T.W. (2019). Langman’s Medical Embryology. 14th Ed. muscle C. superior mediastinum Answer Key: A, E, B, C, False (During the 7th week), C,B,A D. midline close to the hyoid bone (should be external auditory meatus), E, D E. base of the tongue 3. The middle ear cavity A. is of mesodermal origin B. develops from pharyngeal pouch 1 C. develops from pharyngeal arch 1 D. develops from pharyngeal arch 2 E. develops from the otic vesicle 4. Aqueous humor is produced by the A. choroid plexus B. trabecular meshwork C. ciliary processes D. vitreous body E. lens vesicle 5. During the 8th week, cells of the cochlear duct differentiate into the spiral organ of Corti that transduces sound vibrations into electrical signals for hearing. A. True B. False 6. The tympanic cavity originates from which germ layer? A. ectoderm B. mesoderm C. endoderm 7. The malleus and incus are derived from cartilage of the ____, while the stapes is derived from the ____. A. ectoderm, mesoderm B. first pharyngeal arch, second arch C. second arch, first pharyngeal arch D. A: B 8. The eardrum is made up of the following, EXCEPT: A. ectodermal epithelial lining at the bottom of the internal auditory meatus B. endodermal epithelial lining of the tympanic cavity Page 17 of 17 CMED 1D