Pharyngeal Arch Development:

1. Pharyngeal Arch Development: Pamela Knapp, Ph.D. Professor, Dept. Anatomy & Neurobiology MSB1 - Rm. 411 6-7570 peknapp@vcu.edu

2. Branchial arches support the gills, which extract dissolved O2 from ingested water Mammalian branchial apparatus does not fully develop - transformed into head and neck structures. PAs Pharyngeal arches are homologues of branchial arches in fish/amphibians • 4th week, paired, craniocaudal development pattern • 5th rudimentary in humans, 6th not externally visible • Between arches are pharyngeal grooves (clefts) • Neural crest drives appearance of arches

3. What’s in a pharygeal arch? • an aortic arch • a piece of cartilage – derived from neural crest • muscle tissue - derived from original arch mesoderm • a cranial nerve – supplies structures developing from that arch Arch CN 1 V (V2 and V3) 2 VII 3 IX 4 X (superior laryngeal branch) 6 X (recurrent laryngeal branch)

4. Arch organization Floor of pharynx groove pouch Membrane Think of the pharynx as a tube. Imagine rings of tissue being built around the tube, with the outer and inner surfaces of the rings fusing. Because of this, the rings are not isolated. Instead, they are connected and share a“continuous mesenchyme”. There are deep groves between each arch, both externally and internally. A single cell layer of ectodermlines the outside of the arches A single cell layer of endoderm lines the inside of the arches Invaginations between arches on the external surface are pharyngeal grooves (clefts) - lined by ectoderm. Invaginations between arches on the internal surface are pharyngeal pouches - lined by endoderm. The endoderm and ectoderm layers meet between each arch to form a 2 layered pharyngeal membrane. Except for the first membrane, these 2 layers are soon separated (and strengthened!) by mesenchyme.

5. 1 2 3 4 6 G/P/M 1 2 3 4 6 Pharyngeal groove pouch (groove) (Pouches, grooves and membranes take the number of the arch immediately cranial to them.)

6. Artery Cartilage Muscles Nerve Groove Pouch Synopsis of Pharyngeal Arch Transformations

7. PA 1 cartilage is called "Meckel's cartilage” -dorsal: incus, malleus (middle ear ossicles) -intermediate: associated ligaments -ventral: Primordium of the mandible (ie, mandible forms by ossification of mesenchyme around ventral Meckel’s cartilage) PA 2 cartilage is called “Reichert’s cartilage” -dorsal: stapes (middle ear ossicle) -intermediate: associated ligaments/structures -ventral: portions of hyoid bone PA 3 cartilage: forms rest of hyoid bone PA 4 & 6 cartilage: cartilages of the larynx Cartilage transformation • Muscles - Self explanatory - see Table • Nerves - as outlined previously - see Table.

8. Pharyngeal Groove Transformation Only groove with an adult derivative is groove 1. It forms in the area of the otic placode. Tissues from groove 1, the otic placode, arches 1 & 2, and membrane 1 will form external and middle ear structures. Groove (external) will form the external auditory meatus. Lined by ectoderm, since it is formed by a pharyngeal groove. Grooves 2, 3 & 4 are obliterated by external overgrowth of arches 2 and 6. Tissue from arches 2 & 6 grow towards each other, pinching off the 3 grooves as the cervical sinus (lined by ectoderm), which normally obliterates. The external surface, once pocketed by grooves, is now smooth. Overgrowth of archs 2&6 mimics formation of the gill cover (operculum) in fish.

9. Thymus PT4 C-cells PT3 Pharyngeal Pouch& MembraneTransformation Pouch 1 - forms tubotympanic recess, tympanic cavity, auditory (eustachian) tube. Only membrane that forms adult structure is #1 - forms tympanic membrane - strengthened by mesenchyme • Pouch 2: Invaginates to form fossa for the palatine tonsils (tonsils of the oropharynx). • Pouch 3: At least 2 parts. Upper forms inferior parathyroids (PT3 glands). Lower part forms thymus gland. • PT3 movement is driven by movement of thymus, which drags the superior part of pouch 3 with it. • Although there are 2 inferior parathyroid glands in the adult, there is only 1 thymus gland. Right and left primordial thymuses move medially where they fuse. • Pouch 4: At least 2 parts. Upper forms superior parathyroids (PT4 glands). Lower forms ultimobranchial body of the thyroid gland. This initially discrete set of cells breaks up within the thyroid to form areas of C cells which secrete calcitonin. (Some texts say that a 5th pouch forms the ultimobranchial body after being incorporated into the 4th pouch). • The inferior parathyroids start out from a superior location, but end up lower than the PT4 because they migrate further. The parathyroids were named from their adult position.

10. duct Pharynx Pharynx Mesenchyme Mesenchyme duct Outside of Body Outside of Body Cyst Sinus Fistula Branchial Fistula • Persistance of things that should break down Cyst - remnant of duct/groove/pouch - sometimes fluid-filled ex: auricular cyst (1st groove) thyroglossal cyst (thyroglossal duct) Sinus - a pouch or a grooves leaves an opening to the surface ex: external branchial sinus (from persistant cervical sinus to outside) Fistula - opening from outside of body to inside of pharynx. Can involve breakthrough at one or both ends - lack of mesenchyme reinforcement. ex: fistula from side of neck (persistant 2nd groove) through fossa of palatine tonsil (persistant 2nd pouch) ex: failure of mesenchyme to reinforce tympanic membrane Anomalies: Cysts, Sinuses, Fistulas

11. Floor of pharynx Develops from a series of swellings on the floor of the pharynx All swellings are associated with particular pharyngeal arches PA 1: Median tongue bud (tuberculum impar) is site of initial tongue formation. Lateral lingual swellings overgrow tongue bud PA 2: Copula is mostly lost during development. Important in taste bud induction & innervation. PA 3&4: Hypobranchial eminence overgrows copula Merging of tongue prominences makes 2 superficial landmarks - medial sulcus and terminal sulcus Foramen cecum - site of thyroid invagination Development of the Tongue

12. Generalsensory innervation reflects pharyngeal arch derivations • -anterior 2/3 of the tongue is innervated by CN V3 from PA 1. • -posterior 1/3 of the tongue is from CN IX (PA 3) with a small component of • CN X (PA 4) • Specialized sensory organs called taste buds develop mostly on the dorsal surface of the tongue during weeks 11-13. • Taste innervation to the anterior 2/3 of the tongue is by CN VII, via remnants of tissue from copula. Taste innervation to the posterior tongue is mostly by CN IX (some CN X). • Intrinsic tongue muscles are innervated by CN XII, reflecting derivation from migrating occipital somite myoblasts rather than pharyngeal arch tissues. Malformations Tongue innervation • . • Ankyloglossia (tied tongue) - A malformation of the frenulum. Failure of developmental cell death leaves the tongue anchored to the floor of the pharynx • Bifid tongue - A failure of the lateral lingual swellings to merge completely. • Macro- or microglossia- Enlarged or reduced tongue size. Due to abnormal proliferation of mesenchymal tissues within prominences.

13. The thyroid gland is derived from tissue in the floor of the pharynx (endoderm). Late in the 4th week, a mass of endoderm proliferates on the floor of the pharynx at the site of the foramen cecum (sulci interception point). This is the thyroid primordium. Growing thyroid primordium causes a small outpocketing, the thyroid diverticulum. The developing gland tissue descends at the base of an opening it creates, the thyroglossal duct. The duct normally solidifies and obliterates by the 5th week. Part or all of it may persist to form a thyroglossal cyst or sinus. The thyroid continues to descend through tissues of the neck until about week 7. The gland can be active by the 10th week in utero Thyroid Development