Pharyngeal Arches & Development

• The pharyngeal arches contribute to face/palate and brain development

Pharyngeal Arches Overview

• Segmented masses appear ventrolaterally on the occipital and cervical regions of the neck during the 4th week of development
• Typically six pairs of pharyngeal arches appear in humans
• The 5th arch is transient and never fully develops
• Arches surround the rostral end of the foregut, becoming the oral cavity and pharynx in adults
• Arches give rise to structures in the head and neck

Arch Components and Coverings

• Each arch contains an aortic arch, a cartilaginous rod, a muscular component, and a nerve
• Aortic arches are arteries arising from the truncus arteriosus of the primordial heart
• Cartilaginous rods form the skeleton of the arch
• Muscular components differentiate into head and neck muscles
• Nerves supply the mucosa and muscles, derived from the primordial brain's neuroectoderm
• Externally covered by ectoderm and internally lined by endoderm
• Separated by clefts/grooves externally and pharyngeal pouches internally

Cranial Nerve Associations

• Arch 1 is associated with the Trigeminal Nerve (V)
• Arch 2 is associated with the Facial Nerve (VII)
• Arch 3 is associated with the Glossopharyngeal Nerve (IX)
• Arch 4 is associated with the Pharyngeal branches and Superior Laryngeal Nerve of the Vagus Nerve (X)
• Arch 6 is associated with the Recurrent Laryngeal Nerve of the Vagus Nerve (X)

Cartilage/Bone Derivatives

• Arch 1 forms bones of the face like the maxilla, zygoma, mandible, palatine, vomer, squamous part of the temporal bone, incus & malleus as well as the sphenomandibular ligament
• Arch 2 forms the stapes, styloid process, stylohyoid ligament, and the upper hyoid
• Arch 3 forms the lower half and greater horns of the hyoid
• Arch 4 forms the thyroid and epiglottic cartilages of the larynx
• Arch 6 forms the cricoid, arytenoid, and corniculate cartilages of the larynx

Muscle Derivatives

• Muscles derived from pharyngeal arches correspond to their associated cranial nerve
• Arch 1 muscles include muscles of mastication, anterior belly of the digastric, mylohyoid, tensor palatini, and tensor tympani
• Arch 2 muscles include muscles of facial expression, stapedius, and stylohyoid
• Arch 3 muscles include the stylopharyngeus, superior constrictor of pharynx
• Arches 4 and 6 muscles include muscles of the larynx as well as remaining muscles of the pharynx and soft palate

Aortic Arches

• The aortic sac is the rostral common outflow of the developing heart, connecting vessels to the aortic arches
• The truncus arteriosus is a common tube leading to the aortic sac, which forms the ascending aorta and pulmonary trunk
• Structures that arise by birth from the aortic arches include
• 3rd aortic arches form common carotid arteries and proximal portions of the internal carotid arteries
• The left 4th aortic arch forms the aortic arch between left common carotid artery and left subclavian artery
• The right 4th aortic arch forms the proximal portion of the right subclavian artery
• The proximal right and left 6th aortic arches form proximal parts of the right and left pulmonary arteries
• The distal left 6th aortic arch forms the ductus arteriosus which becomes ligamentum arteriosum
• The aortic sac, associated with 4th arch forms the ascending aorta, part of arch of aorta, right brachiocephalic artery

Pharyngeal Pouches

• 1st pharyngeal pouch becomes the auditory tube and middle (tympanic) ear cavity
• 2nd pharyngeal pouch develops into the epithelium of the palatine tonsils
• 3rd pharyngeal pouch subdivides- the superior component migrates to become the inferior parathyroids and the other inferior component migrates to become the thymus
• 4th pharyngeal pouch subdivides- the superior component migrates to become the superior parathyroids and the inferior component migrates to become the C cells of the thyroid

Face and Palate Development

• The face develops from 5 prominences (swellings) around the stomodeum
• These include a frontonasal prominence, 2 maxillary prominences, and 2 mandibular prominences
• The maxillary and mandibular prominences are derived from pharyngeal arch 1

Face Development

• During week 5, the frontonasal prominence develops 2 thickenings near its lateral edges- the nasal placodes
• By week 6, each nasal placode develops a depression in its center called a nasal pit
• The nasal pit will form the anterior nasal openings and nasal cavity
• The part of the nasal placode lateral to the nasal pit becomes the lateral nasal process (prominence)
• The part medial to the nasal placode becomes the medial nasal process (prominence)
• A nasolacrimal furrow (groove) is formed at the juntion of the maxillary prominence and the lateral nasal process as the embryo develops
• A solid rod of cells is formed from the ectoderm cells that detaches from the groove, and becomes the nasolacrimal duct, which drains tears from the orbit to the inferior meatus of the nasal cavity
• In normal fetal development fusion of the maxillary process and the lateral nasal process occurs forming an overlying skin and the surface ectoderm rod sinks deep and it should canalize prior to birth
• Failure of fusion of the maxillary prominence and lateral nasal process results in an oblique facial cleft
• The two medial nasal processes fuse with one another during week 7 to form the intermaxillary segment
• The intermaxillary segment is the precursor to the philtrum of the lip
• Failure to fuse results in a median cleft lip associated with brain anomalies
• The intermaxillary segment (from the two medial nasal prominences) and maxillary prominences fuse during week 7, forming the upper lip and jaw architecture.
• Failure to fuse forms a cleft lip that might be unilateral or bilateral.

1st Arch Syndrome

• "Treacher Collins Syndrome"
• Failure of neural crest cells into the 1st arch
• Underdeveloped zygomatic bones, mandibular hypoplasia, and malformed ears
• Hearing loss
• No significant cognitive deficit

Nasal Cavity Formation

• Formed by continued invagination of the nasal pits and continued growth of surrounding prominences
• The pits fuse to form a single nasal sac and a common nasal cavity
• Initially separated from the stomodeum and oral cavity by an oronasal membrane that breaks down around week 4
• The secondary palate eventually separates those definitive spaces

Palate Development

• The palate develops from mesenchyme tissue deep to the intermaxillary segment and the maxillary processes
• The portion derived from the intermaxillary process (median palatine process) will form the anterior (primary) palate
• The tissue deep to the maxillary process (lateral palatine processes) forms the posterior (secondary) palate

Palate Formation

• The intermaxillary (premaxillary) segment will form first, becoming the portion of the hard palate rostral to the incisive foramen
• It is the source of the incisor teeth
• The developing nasal cavity is initially open to the oral cavity caudal to the primary palate
• The secondary palate forms later from 2 palatine shelves (extensions of the maxillary prominences.)
• As the secondary palate forms, the frontonasal prominence's underlying mesenchyme invaginates to form the nasal septum
• The tissue then meets the medially growing secondary palates in the midline to complete the separation of the oral cavity from the nasal cavity
• The palatine shelves are originally on either side of the tongue
• The tongue moves downward in the seventh week of gestation, and the lateral processes grow medially
• The fusion of the hard palate begins anteriorly and continues posteriorly during the eighth week
• The nasal septum grows ventrally to fuse with the forming palate between the 9th and 12th weeks
• Incomplete fusion of the palatine shelves can lead to a bifid uvula/soft palate and/or cleft palate

Tongue Development

• The line of fusion of the oral and pharyngeal parts of the tongue is indicated by the terminal sulcus
• This is a V-shaped groove immediately posterior to the circumvallate papillae
• Structures associated with the tongue are;
• Arch 1 forms the medial andlateral tongue buds, which becomes the anterior 2/3 of the adult tongue
• Arches 2 to 4 form the copula & hypobranchial eminence, which forms the posterior 1/3 of the adult tongue

Nervous System Development Terminology

• Neurulation: Formation of the neural tube and the eventual formation of the central nervous system
• Neural plate: Differentiation and thickening of the ectoderm overlying the notochord around day 17 (before somites)
• Neural groove: Invagination of the neural plate
• Neural tube: Fusion of the edges of the neural groove
• Ectoderm then separates from the nervous tissue
• Mesenchymal cells infiltrate between the two layers
• Neural crest cells: Cells at the crest of the neural folds specialize and migrate from the neural ectoderm into the deeper mesoderm

Neural Tube Formation

• Anterior and Posterior Neuropores: cranial and caudal ends of the neural tube open to the amniotic cavity
• Anterior neuropore closes around day 25, and the posterior neuropore closes at about day 27
• Failure of anterior neuropore closure - Exencephaly (rare cephalic disorder, nervous system)
• Failure of posterior neuropore to close - Spina Bifida
• Conditions can vary from very mild symptoms to severe symptoms

Derivatives of Neural Crest Cells

• Derivatives include spinal, autonomic and cranial nerve ganglia; Schwann cells (myelinating cells of the peripheral nervous system); medulla of the adrenal gland; meninges (arachnoid & pia mater tissue covering of the central nervous system); pigment cells of the skin; glial cells; C cells of thyroid; conotruncal region of the heart; connective tissue, some bones, dermis of head & neck

Brain Development

• 3 primary vesicles appear at 4 weeks
• 5 secondary vesicles appear at 5 weeks
• Structures include
• Prosencephalon which at the 5 vesicle stage of dev is split into the Telencephalon and Diencephalon.
• The Telencephalon becomes the Cerebrum and the Diencephalon becomes the Thalamus/hypothalamus
• Mesencephalon at the 5 vesicle stage of dev remains the Mesencephalon and becomes the Midbrain
• Rhombencephalon which at the 5 vesicle stage of dev is split into Metencephalon and Myelencephalon.
• The Metencephalon becomes the Pons/cerebellum and the Myelencephalon becomes the Medulla