Development of pharyngeal arches Flashcards
At what days do Pharyngeal arches begin to form?
Arch 1 + 2 - about 25 days
Arch 3 - about 28 days
What develops from pharyngeal arch 1?
Early face/jaw from frontonasal prominence 1st pharyngeal arch
What does each arch contain?
Each arch has a mesenchyme core that forms;
- cartilage element
- muscle
- artery
- cranial nerve
Pharyngal clefts which are external (ectoderm)
Pharyngeal pouches which are internal (endoderm)
Each cleft/pouch takes its number from the arch rostral to it
What is each arch derived from and what do these make?
Each arch is derived from;
1). Mesoderm
2). Neural crest
3). Ectoderm
Paraxial mesoderm (paraxial = midline)- muscle/bvs plus others (some goes to pharyngeal arches from somitomeres (arch 1-3), somites (arch 4,6)
Lateral plate mesoderm - (trapezius + sternocleidomastoid plus small contribution to cartilages)
Neural crest - bone, most cartilage (ventral flow around placodes (surface thickenings) and into pharyngeal arches)
Ectodermal placodes (thickening of ectoderm that gives rise to sensory neurons/ganglia)
What nerves supply each pharyngeal arch?
arch 1: CN V (trigeminal) - Opthalamic, maxillary and mandibular branches
arch 2: CN VII (facial)
arch 3: CN IX (glossopharyngeal)
arch 4: CN X Vagus (superior laryngeal branch of the vagus)
arch 6: CN X Vagus (recurrent laryngeal branch of the vagus)
What forms from each arches paraxial mesoderm?
Arch 1 - mastication
Arch 2 - facial expression
Arch 3 - stylopharyngeus (somitomeres)
Arch 4 - 6 - constrictors, lev v palatini, Cricothyroid (somites)
What blood vessels form from which arches?
Arch 1 - External carotid
Arch 2 -
Arch 3 - Internal carotid, common carotid
Arch 4 - Aortic arch (from Left of 4th), Right subclavian artery (from Right of 4th)
Arch 6 - Ductus ateriosus (from left of 6th), Left pulmonary artery (from left of 6th), Right pulmonary artery (from right of 6th)
More arteries come of each arch but they undergo differential loss and are not seen once fully grown
What are the different derivatives of cartilaginous components ?
Derivatives of cartilaginous components (neural crest mesenchyme; laryngeals from lateral plate mesoderm)
1st Arch- Meckel’s cartilage (soon disappears), Malleus and Incus
2nd Arch - Stapes, Styloid process, Stylohyoid ligament, Lesser horn of hyoid bone, 1/2 Body of hyoid bone
3rd Arch - 1/2 Body of hyoid bone, Greater horn of hyoid bone
4th Arch - Thyroid cartilage
6th - Cricoid cartilage
Why do humans not have a 5th pharyngeal arch?
As this arch only makes structures in animals, not in humans
How does the pharyngeal arch cartilage help in the formation of bones in the face and neck?
Review image
What does the 1st pharyngeal arch do ?
Image
What does the 2nd pharyngeal arch do ?
Image
What does the 3rd pharyngeal arch do?
Image
What do the 4th and 6th pharyngeal arches do?
Image
What does the paraxial mesoderm form ?
All voluntary muscles, arteries, neurocranium, meninges, dorsal dermis
What does the lateral plate mesoderm form?
Laryngeal cartilages; Regional connective tissue
What does the neural crest form?
- Pharyngeal arch skeleton
- Viscerocranium
- Glandular connective tissue
- Few parts of the neurocranium, teeth, interact with ectodermal placodes for ganglia formation
What do the Ectodermal placodes form?
With neural crest to form neurons of sensory ganglia (V, VII, IX and X) also sensory apparatus (eyes/nose not shown)
What do the different pouches form?
Pouches form as invaginations of endoderm in the lateral walls of the pharynx
1- Primative tympanic cavity (auditory tube)
2 - Palatine tonsil/tonsillar fissure
3 - Parathyroid (inferior) and thymus (migrates down to neck)
4 - Parathyroid gland superior and Ultimobranchial body (parafollicular C cells of thyroid - Calcitonin secreting cells) - can get ectopic thymus
Floor will form the tongue
Posterior top the tongue is the laryngeal orifice
How does the thymus, parathyroid glands and ultimobranchial body migrate ?
See image for migration order:
Thymus can remain in neck (ectopic thymus)
Inferior parathyroid can be variable in position (ectopic parathyroid)
What do the pharyngeal clefts form?
Pharyngeal clefts;
1st Cleft - Dorsal part of 1st cleft gives rise to the external auditory meatus and external part of tympanic membrane. Deepest part gives rise to the tympanic membrane (ear drum)
2nd arch proliferates and overgrows 3rd and 4th arches
2nd, 3rd and 4th clefts lose contact with exterior forming cervical sinus - after losing connection with exterior the cervical sinus usually disappears - But can stay - if you have a lump along sternocleidomastoid have to rule out tumour but could be this
What pharyngeal cleft (branchial cleft) abnormalities can cause congenital disease of the neck?
Pharyngeal cleft (branchial cleft) abnormalities commonest congenital disease of the neck?
- Cyst (adults) and fistulas/sinuses (children)
- Anterior to sternocleidomastoid
- Diagnostic challenge, presume cancerous until proven otherwise
Explain neural crest migration?
Molecular determination - Neural crest migration from rhombomeres
3 streams of neural crest cells migrate from segments of hindbrain called Rhmobomeres
Carry expression of homeodomain containing transcription factor OTX and HOX genes into pharyngeal arches
Provide guidance cues for cranial nerves growing back from ganglia
Neural crest cells migrate into arch carrying (OTX/HOX) codes
Neural crest cells respond to local patterns endoderm signals (FGF, BMP, PAX, SHH)
This then specifies mesenchymal expression pattern and arch characteristics
How common are Craniofacial defects and how do we think they happen?
Craniofacial defects;
- Congenital defects 3-5% of live births
- 1/500 - 1/1000 births with craniofacial abnormalities
- Many involve perturbed signals involving the neural crest (migration, proliferation, differentiation)
What is Treacher Collins Syndrome ?
Treacher Collins Syndrome (autosomal dominant 1/50,000)
First/second arch syndrome
- Defective protein called Treacle (TCOF1 gene)
- Failure of formation/apoptosis of neural crest cells and migration into first and second pharyngeal arches
- Abnormal eye shape
- Micrognathia
- Conductive hearing loss
- Underdeveloped zygoma
- Malformed ears
What is Di George Syndrome ?
Di George Syndrome (also called 22q11 deletion syndrome, congenital thymus hypoplasia, or third and fourth pharyngeal pouch syndrome)
3rd and 4th pouches fail to develop and thymus and parathyroids are defective
Also known as a CATCH-22 disorder;
C - Cardiac abnormality (especially tetralogy of Fallot)
A - Abnormal facies (more frequency cleft lip and palate, small jaw, small upper lip, eyes slanted upward/downwarrd, low-set abnormal folding ears
T - Thymic aplasia (issues with immune)
C - Cleft palate
H - Hypocalcemia
22- deletion in chromosome 22 - unusually denovo
What is Sonic Hedgehog syndrome?
Sonic hedgehog (SHH) in craniofacial patterning - holoprosencephalon spectrum
SHH governs the width of facial features (on a scale)
On the lower end you have inadequate SHH function and this causes narrowing and fusion (low dose eyes and mud structures fuse). In severe cases get cyclopia (1 eye - Cyclops)
Mid cases can get signal median incisor, no philtrum
On the higher end you get excess SHH function which causes widening structures and duplication. Get Diprosopus
What are craniosynotosis syndromes ?
Craniosynotosis syndromes (e.g Apert and Crouzon syndromes) (genetic causes, mutations - FGFR’s, TWIST transcription factor, EPHRIN-B1
Example;
FGFR2 and FGFR3 mutations and craniosynostosis
- Mutations cause a gain of function -> constitutive activation of receptors
- FGF signalling activates bone calficiation and reduces cell proliferation in the mesenchyme at the suture - generating premature fusions
- Premature fusion (amongst other affects such as syndactaly) results
What are craniosynotosis syndromes ?
Craniosynotosis syndromes (e.g Apert and Crouzon syndromes) (genetic causes, mutations - FGFR’s, TWIST transcription factor, EPHRIN-B1
Example;
FGFR2 and FGFR3 mutations and craniosynostosis
- Mutations cause a gain of function -> constitutive activation of receptors
- FGF signalling activates bone calficiation and reduces cell proliferation in the mesenchyme at the suture - generating premature fusions
- Premature fusion (amongst other affects such as syndactaly) results
Mutations spontaneous in the paternal line, increase with age
