EMBRYOLOGY LC7 Systems-Based Embryology PDF

The skull of the head ○ VISCEROCRANIUM (Face) OUTLINE...

The skull of the head ○ VISCEROCRANIUM (Face) OUTLINE ○ NEUROCRANIUM (Protective case around the brain) I. SYSTEMS-BASED EMBRYOLOGY II. PHARYNGEAL ARCHES III. PHARYNGEAL POUCHES IV. PHARYNGEAL CLEFTS A. Birth Defects Involving the Pharyngeal Region V. TONGUE VI. THYROID GLAND VII. FACE VIII. TEETH IX. EAR X. EYE I. SYSTEMS-BASED EMBRYOLOGY The axial skeleton includes the skull, vertebral column, ribs and sternum consisting your leverage The skeletal system develops from paraxial and lateral plate (parietal layer) mesoderm and from neural crest. Figure 2. Skeletal structures of the head and face. Mesenchyme for these Paraxial mesoderm forms segmented series of tissues on each side of structures is derived from neural crest [blue], lateral plate mesoderm [yellow], neural tube, known as SOMITOMERES in the head region and and paraxial mesoderm [somites and somitomeres] [red]. SOMITES in the occipital region caudally. SOMITES differentiate into SCLEROTOME in ventromedial part, DERMOMYOTOME in dorsolateral part II. PHARYNGEAL ARCHES At the end of 4th week, sclerotome become polymorphous and form loosely organized tissue called MESENCHYME or EMBRYONIC CONNECTIVE TISSUE Most distinctive feature in the development of head and neck Majority of the muscles and tissues originate from the mesenchyme. ○ Also called BRANCHIAL ARCHES, resemble the gills It is characteristic for mesenchyme (Mesenchymal stem cells (MSCs) (branchia) of a fish are multipotent stem cells) to migrate and differentiate in many ways ○ Appear in the 4th & 5th weeks of development and ○ FIBROBLASTS (contributes to the formation of connective contribute to the characteristics external appearance of tissues) the embryo ○ CHONDROBLASTS (formation of cartilage cells) Each pharyngeal arch has its own arterial component, characterized ○ OSTEOBLASTS (bone cells; flat bones) by its own muscular components, have their own cranial nerve and ○ MYOCYTES (muscle cells) whenever the muscle cells migrate, they carry their nerve ○ ADIPOCYTES (fat cells that give rise to marrow adipose compartment. tissue) Anything that connects you to the outside world originates from the ectoderm Anything that is connected to your leverage (connective tissues, skeleton, muscles, etc) originates from the mesoderm Organs originate from the endoderm Figure 3. Development of the pharyngeal arches A. 25 Days B. 28 Days, C. 5 weeks Pharyngeal arches start as first and second pharyngeal arches at 25 days with cranial and caudal neuropore still open. At 28 days the Figure 1. Migration pathways of neural crest cells from forebrain, midbrain, and pharyngeal arches are now more marked and at the 5th week it is hindbrain regions into their final locations [blue areas] in the pharyngeal arches developed into a pharyngeal cleft which will then form the head and and face. Regions of ectodermal thickenings [epipharyngeal placodes], which neck. will assist crest cells in formation of the fifth [V], seventh [VII], ninth [IX], and Caudal neuropore will form the extremities. tenth [X] cranial sensory ganglia. Page 1 of 7 [EMBRYOLOGY] 1.07 Systems-Based Embryology: Head, Neck, Eyes, & Ears – Dr. La Paz L. Peredo, MD Figure 4. A) Development of the pharyngeal clefts and pouches. The second arch grows over the third and fourth arches, burying the second, third, and fourth pharyngeal clefts. B) Remnants of the second, third, and fourth pharyngeal clefts form the cervical sinus, which is normally obliterated. Note the Table 1. Derivatives of the Pharyngeal Arches and their Innervation structures formed by the various pharyngeal pouches. First pharyngeal arch: maxilla to mandible to ear (from lower portion of head upwards) Second pharyngeal arch: bone below the mandible (hyoid); responsible for equilibrium (stapes bone) Third and fourth pharyngeal arch: responsible for the tongue III. PHARYNGEAL POUCHES Human embryo has 4 pairs of pharyngeal pouches; the 5th is rudimentary First pharyngeal pouch: tubotympanic recess (stalklike diverticulum) - distal portion 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 Table 2. Derivatives of the Pharyngeal Pouches eardrum. Second pharyngeal pouch: epithelial lining proliferates and forms buds that penetrate into the surrounding mesenchyme. The buds are IV. PHARYNGEAL CLEFTS secondarily invaded by mesodermal tissue, forming the primordium of the palatine tonsils. During the 3rd and 5th months, the tonsil is Of 4 pharyngeal clefts, only 1 contributes to the definite structure of infiltrated by lymphatic tissue. Part of the pouch remains and is the embryo found in the adult as the tonsillar fossa. ○ The dorsal part of the 1st cleft penetrates the Third pharyngeal pouch: together with the fourth pouches, they are mesenchyme and gives rise to external auditory meatus characterized at their distal extremity by a dorsal and a ventral wing. (EAM) forming the EARDRUM In the 5th week, epithelium of the dorsal region of the third pouch differentiates into the inferior parathyroid gland, whereas the Birth Defects Involving the Pharyngeal Region: ventral region forms the thymus. Growth and development of the thymus continue until puberty. In the young child, the thymus 1. Branchial Fistulas occupies considerable space in the thorax and lies behind the Occur when the 2nd pharyngeal arch fails to grow sternum and anterior to the pericardium and great vessels. In older caudally over the 3rd and 4th arches, leaving remnants of persons, it is difficult to recognize because it is atrophied and the 2nd, 3rd and 4th clefts in contact with the surface by replaced by fatty tissue. The parathyroid tissue of the third pouch a narrow canal → LATERAL CERVICAL CYST (lateral aspect comes to rest on the dorsal surface of the thyroid gland and forms of the neck directly anterior to the sternomastoid muscle the inferior parathyroid gland. just below the angle of the jaw); not visible at birth but Fourth pharyngeal pouch: Epithelium of the dorsal region forms the becomes evident as it enlarges during childhood. superior parathyroid gland. When the parathyroid gland loses Internal branchial fistula: RARE; Cervical sinus is contact with the wall of the pharynx, it attaches itself to the dorsal connected to the lumen of the pharynx by a small canal, surface of the caudally migrating thyroid as the superior parathyroid which usually opens in the tonsillar region. Results from gland. The ventral region gives rise to the ultimobranchial body, the rupture of the membrane between the 2nd which is later incorporated into the thyroid gland. Cells of the pharyngeal cleft and pouch at some time during ultimobranchial body give rise to the parafollicular cells, or C cells, of development. the thyroid gland. These cells secrete calcitonin, a hormone involved in regulation of the calcium level in the blood. Page 2 of 7 [EMBRYOLOGY] 1.07 Systems-Based Embryology: Head, Neck, Eyes, & Ears – Dr. La Paz L. Peredo, MD Figure 7. A patient with Goldenhar Syndrome. Figure 5. Patient with a lateral cyst. These cysts are always on the lateral side of the neck in front of the sternocleidomastoid muscle. They commonly lie under the angle of the mandible and do not enlarge until later in life. V. TONGUE 2. Robin Sequence May occur independently or in association with other Originating from the 1st pharyngeal arch, it appears in embryos of syndromes and malformations approximately 4 weeks in the form of 2 lateral lingual swelling and 1 Alters 1st arch structure with development of mandible medial swelling, the tuberculum impar; sensory innovation is most severely affected supplied by the mandibular branch of Trigeminal nerve. Triad of micrognathia (small mandible), cleft palate and Posterior part or root of the tongue originates from the 2nd, 3rd and glossoptosis (posteriorly placed tongue) 4th pharyngeal arch; sensory innervation is supplied by the glossopharyngeal nerve Copula (hypobranchial eminence): second median swelling formed by mesoderm of the 2nd-3rd and a part of the 4th arch. Third median swelling: posterior part of the 4th arch, marks development of the epiglottis. Immediately behind this swelling is the laryngeal orifice, which is flanked by the arytenoid swellings. Body of the tongue: anterior two-thirds of tongue; formed as the lateral lingual swellings increase in size, overgrowing the tuberculum impar and merge. Because the mucosa covering the body of the tongue originates from the 1st pharyngeal arch, sensory innervation to this area is by the mandibular branch of the trigeminal nerve. The body of the tongue is separated from the posterior third by a V-shaped groove, the terminal sulcus. Root of the tongue: posterior part of tongue; originates from the 2nd-3rd and a part of the fourth pharyngeal arch; supplied by the glossopharyngeal nerve Epiglottis and the extreme posterior part of the tongue: innervated by the superior laryngeal nerve. Some of the tongue muscles probably differentiate in situ, but most are derived from myoblasts originating in occipital somites. Thus, tongue musculature is innervated by the hypoglossal nerve. General sensory innervation of the tongue: body is supplied by the trigeminal nerve, the nerve of the 1st arch; root is supplied by the glossopharyngeal and vagus nerves, the nerves of the 3rd and 4th Figure 6. Patients with craniofacial defects are thought to arise from insults to arches. the neural crest cells. A) Robin sequence. B and C) DiGeorge Syndrome. D) Special sensory innervation (taste): the anterior ⅔ of the tongue is Hemifacial microsomia. provided by the chorda tympani branch of the facial nerve; the posterior 3rd is supplied by the glossopharyngeal nerve. 3. Oculoauriculovertebral Spectrum (Goldenhar Syndrome) Craniofacial abnormalities that usually involve the maxillary temporal and zygomatic bones Abnormal ear, small chin, tumors, in the eye and fused vertebral Page 3 of 7 [EMBRYOLOGY] 1.07 Systems-Based Embryology: Head, Neck, Eyes, & Ears – Dr. La Paz L. Peredo, MD Maxillary prominences can be distinguished lateral to the stomodeum, and mandibular prominences can be distinguished caudal to this structure. Frontonasal prominence, formed by proliferation of mesenchyme ventral to the brain vesicle, constitutes the upper border of the stomodeum. On both sides of the frontonasal prominence, local thickenings of the surface ectoderm, the nasal (olfactory) placodes, originate under inductive influence of the ventral portion of the forebrain (See Figure 10). During the 5th week, the nasal placodes invaginate to form nasal pits. They will then create a ridge of tissue that surrounds each pit and forms the nasal prominences. The prominences on the outer edge of the pits are the lateral nasal Figure 8. Ventral portion of the pharyngeal arches seen from above showing prominences; those on the inner edge are the medial nasal development of the tongue. I to IV, the cut pharyngeal arches. A. 5 weeks [~6 prominences (See Figure 11). mm]. B. 5 months. Note the foramen cecum, site of origin of the thyroid primordium. ANKYLOGLOSSIA (Tongue-tie) - The tongue is not freed from the floor of the mouth - the normal tongue is connected to the floor of the mouth posteriorly - However, in ankyloglossia, the tongue is connected up to the tip, with the frenulum extended up to the tip. Figure 10. A) Lateral view of an embryo at the end of the fourth week, showing position of the pharyngeal arches. B) Frontal view of a 4.5-week embryo Figure 9. Ankyloglossia (Tongue-tie) showing the mandibular and maxillary prominences. The nasal placodes are visible on either side of the frontonasal prominence. C) Scanning electron micrograph of a human embryo at a stage similar to that of B. VI. THYROID GLAND The thyroid gland appears as an epithelial proliferation in the floor of the pharynx between the tuberculum impar and the copula; later indicated by the foramen cecum. Descends in front of the pharyngeal gut as a bilobed diverticulum. During this migration, the thyroid remains connected to the tongue by a narrow canal, the thyroglossal duct. This duct later disappears. With further development, the thyroid gland descends in front of the hyoid bone and the laryngeal cartilages until reaching its final position in front of the trachea in the 7th week. By then, it has acquired a small median isthmus and two lateral lobes. Figure 11. Frontal aspect of the face. A) 5-week embryo. B) 6-week embryo. The thyroid begins to function at approximately the end of the 3rd The nasal prominences are gradually separated from the maxillary prominence month, at which time the first follicles containing colloids become by deep furrows. visible. Follicular cells produce the colloid that serves as a source of thyroxine and triiodothyronine. Parafollicular Cells, or C cells, derived from the ultimobranchial body serve as a source of calcitonin. VII. FACE At the end of 4th week, facial prominences formed mainly by the 1st pair of pharyngeal arch appear Page 4 of 7 [EMBRYOLOGY] 1.07 Systems-Based Embryology: Head, Neck, Eyes, & Ears – Dr. La Paz L. Peredo, MD Table 3. Structures Contributing to Formation of the Face Note: the face originated from the 1st pharyngeal arch, innervated by the trigeminal nerve (MESODERMAL) Facial Clefts ○ Cleft lip and cleft palate are common defects that result in abnormal facial ○ Due to partial or complete lack of fusion of the maxillary prominence on one side or both sides Figure 14. A) Lateral cleft lip. B) Bilateral cleft lip. C) Cleft palate. D) Midline cleft lip. VIII. TEETH Develop from epithelial-mesenchymal interactions between oral epithelium and neural crest-derived ○ Enamel is made by ameloblasts ○ Densin is produced by odontoblasts ○ Cementum is formed by cementoblasts Deciduous teeth or milk teeth appear 6-24 months after birth. Permanent teeth of definitive teeth supplant the milk teeth, forming during the 3rd month of development Tooth Abnormalities ○ Abnormal in number, shape and size Figure 12. Photographs demonstrating normal and abnormal development ○ Discolored by Tetracycline involving the midline of the face and brain. A) Normal face of an embryo at the ○ Deficient in enamel (Rickets) caused by Vitamin D beginning of the sixth week. Note the distance between the nasal openings deficiency (vertical lines) and between the medial nasal prominences (Xs). B) Face of a newborn with a midline cleft lip. In this case, there is insufficient tissue in the midline to fill in the space between the medial nasal prominences. IX. EAR consists of 3 parts that have different origins but function as one unit ○ internal ear ○ middle ear ○ external ear INTERNAL EAR Originates from the otic vesicle, in the 4th week of development detaches from surface ectoderm ventral component of otic vesicle give rise to saccule and cochlear duct dorsal component gives rise to utricle canals, semilunar canals, and endolymphatic duct ○ membranous labyrinth involved in equilibrium MIDDLE EAR Consist of tympanic cavity and auditory tube lined with epithelium of endodermal origin derived from 1st Figure 13. Ventral view of the palate, gum, lip, and nose. A) Normal. B) pharyngeal pouch Unilateral cleft lip extending into the nose. C) Unilateral cleft involving the lip ossicles transfer sound from tympanic membrane to the oval window and jaw and extending to the incisive foramen. D) Bilateral cleft involving the lip derived from the 1st (malleus, incus) and 2nd (stapes) pharyngeal and jaw. E) Isolated cleft palate. F) Cleft palate combined with unilateral anterior arches cleft lip. Page 5 of 7 [EMBRYOLOGY] 1.07 Systems-Based Embryology: Head, Neck, Eyes, & Ears – Dr. La Paz L. Peredo, MD EXTERNAL EAR auricle develops from the 1st pharyngeal cleft, separated from the tympanitic cavity by the tympanic membrane (ear drum) the eardrum consists of: ○ ectodermal epithelial lining ○ intermediate layer of mesenchyme ○ endodermal lining from the 1st pharyngeal pouch External ear defects: ○ common; can be minor or severe abnormalities ○ all of the frequently occurring chromosomal syndromes and most of the less common ones have ear anomalies as one of their characteristics. Figure 16. Coloboma ○ Congenital cataract Lens opacity during intrauterine life Risk factors: German measles during 4th-7th week AOG Associated with hearing loss Because of the MMR (measles, mumps, and rubella) vaccine, congenital rubella syndrome has been nearly eradicated in the US. Figure 15. External ear defects. A) Almost complete absence (anotia) of the external ear. B) A small ear (microtia) with abnormal features. C) Abnormal ear with preauricular appendages (skin tags). Note also the slight depression and small hillock along the line of the mandible. These are the remnants of ear development and indicate the path of the ear as it moved to its normal position due to growth of the mandible. D) Preauricular pit. Figure 17. Congenital cataract X. EYE ○ Microphthalmia eye is too small begin to develop as a pair of outpocketings that will become the eyeball may be only two thirds of its normal optic vesicles on each sides of the forebrain at the end of the 4th volume week of development associated with other ocular abnormalities optic vesicles contact the surface ectoderm and induce lens can result from intrauterine infections such as formation cytomegalovirus and toxoplasmosis Eye abnormalities: ○ Coloboma may occur if the choroid fissure fails to close. When it does not, a cleft persists. Although such a cleft is usually in the iris only – coloboma iridis. Can extend to the ciliary body, retina, choroid, optic nerve, eyelids Coloboma is a common eye abnormality frequently associated with other eye defects PAX2 gene mutation. Renal defects also occur with mutations in PAX2 as part of the renal coloboma syndrome. Figure 18. Microphthalmia Page 6 of 7 [EMBRYOLOGY] 1.07 Systems-Based Embryology: Head, Neck, Eyes, & Ears – Dr. La Paz L. Peredo, MD ○ Anophthalmia absence of the eye TEST YOUR KNOWLEDGE accompanied by severe cranial abnormalities 1. Embryonic cells that contribute to the formation of connective tissue. 2. This type of cell differentiate into different types of cells. 3. Pharyngeal arches are derived from these except: A. Ectoderm B. Endoderm C. Mesoderm D. Neural crest E. All of the above F. None of these 4. Part of the pharyngeal pouch that will give rise to the ear 5. Part of the ear that originates from the 1st pharyngeal pouch, and is separated from the tympanic cavity by the tympanic membrane. A. Inner Ear B. Middle Ear C. External Ear 6. Which of the following precursor cells will form enamel? A. Enameloblasts B. Ameloblasts C. Odontoblasts D. Cementoblasts Figure 19. Anophthalmia 7. Choose the correct match A. Pharyngeal pouch 2: Thymus and Inferior parathyroid glands ○ Congenital aphakia and aniridia B. Pharyngeal pouch 4: Palatine tonsils and Tonsillar fossa aphakia (absence of the lens), aniridia C. Pharyngeal pouch 1: Tympanic cavity (absence of the iris) 8. A developmental eye defect that is caused by a failure in closing of the rare anomalies that results from disturbances choroid fissure. in induction and development of tissues 9. Mesenchyme for the formation of the head region is derived from: responsible for formation of these structures A. paraxial mesoderm mutations in PAX6 result in aniridia B. lateral plate mesoderm C. neural crest cells D. all of the above 10. Which part of the ear is the sound collecting organ? A. Middle ear B. External ear C. tympanic membrane D. Internal ear Figure 20. Aniridia Answers: 1.Fibroblasts, 2. Multipotent stem cells, 3. F, 4. First pharyngeal pouch, 5. C, 6. B, 7. C, 8. Coloboma, 9. D, 10. A ○ Cyclopia (one eye) and Synophthalmia (fused eyes) a spectrum of defects in which the eyes are partially of completely fused REFERENCES Loss of midline tissue that may occur as early as days 19 to 21 of gestation or at later stages Sadler, T. W., et.al. (2019). Langman's medical embryology (14th ed.). Lippincott when facial development is initiated. Williams & Wilkins. This loss results in the underdevelopment of Katzung, B. G. (2017). Basic and clinical pharmacology (14th ed.). McGraw-Hill the forebrain and frontonasal prominence. Education. Peredo, L.P. PPT Lecture Figure 20. Synophthalmia Page 7 of 7