Introduction / Pharyngeal Arches

Key questions

1. Q1When are arches 1 and 2 first present, and what else is visible then?

   Weeks 3–3.5. The three germ layers, the pericardial bulge, and the cranial and caudal neuropores are also present.
2. Q2When do arches 3, 4 and 6 become visible?

   Week 5.
3. Q3By what week are arches, pouches and clefts fully formed, and what does each arch gain then?

   Weeks 5.5–6. Each arch becomes separately innervated and gets its own artery.
4. Q4When does Meckel's cartilage appear, and when does it disappear?

   It fills the mandibular process by week 4.5 and disappears around week 8, except the two dorsal remnants that become the incus and malleus.

Key questions

1. Q5Which four cell types populate an arch, and how many tissue types do they come from?

   Mesenchyme, ectoderm, endoderm and neural crest, from three tissue types. Neural crest is itself derived from ectoderm.
2. Q6Which mesoderm fills the arch core, and what does it build?

   Paraxial and lateral plate mesoderm. It builds the muscles of the face and neck, and each arch has its own population, so each arch has its own muscles.
3. Q7What is neural crest predetermined to form, and when and where does it migrate from?

   The skeletal component of the face. It migrates at weeks 4.5–5 from the hindbrain, midbrain and, less so, the forebrain.
4. Q8How do you tell a pouch from a cleft?

   A pouch is an indentation on the inside, over endoderm. A cleft is an indentation on the outside, over ectoderm.

Key questions

1. Q9What are the cartilage, skeletal derivatives, muscles and nerve of arch 1?

   Meckel's cartilage → malleus and incus. Maxillary process neural crest → premaxilla, maxilla, zygomatic, part of temporal bone. Muscles of mastication, anterior digastric, mylohyoid, tensor tympani, tensor palatini. CN V3.
2. Q10Is the mandible made from Meckel's cartilage?

   No. The mandible forms from the mesenchyme and neural crest that surround Meckel's cartilage, which only serves as a template.
3. Q11Which parts of the hyoid come from arch 2 and which from arch 3?

   Arch 2: lesser horn and upper body. Arch 3: greater horn and lower body.
4. Q12What is the only muscle of arch 3, and its nerve?

   Stylopharyngeus, innervated by CN IX.
5. Q13What one-word theme goes with each arch?

   Arch 1: chewing (+ ossicles). Arch 2: facial expression. Arch 3: swallowing. Arches 4 and 6: larynx and pharynx.
6. Q14Why should you never pick "arch 5" as an answer?

   Arch 5 never forms or regresses completely, so it has no derivatives.
7. Q15Which vagal branch serves arch 4 vs arch 6, and where do the laryngeal cartilages come from?

   Arch 4: superior laryngeal. Arch 6: recurrent laryngeal. The laryngeal cartilages come from lateral plate mesoderm, not neural crest.
8. Q16A patient can't wrinkle their forehead and has hyperacusis. Which arch's muscles are affected?

   Arch 2 (CN VII): muscles of facial expression and stapedius.

Key questions

1. Q17What does pouch 1 form, and why is it unique among the pouches?

   The tubotympanic recess → tympanic cavity (distal) and eustachian tube (proximal). It is the only pouch that contacts ectoderm (cleft 1).
2. Q18What does pouch 2 form, and what happens to it by month 4?

   The palatine tonsils. The center of the bud undergoes apoptosis, leaving the tonsillar crypt, which fills with lymphoid tissue.
3. Q19What do the dorsal and ventral wings of pouch 3 form?

   Dorsal wing: inferior parathyroid. Ventral wing: thymus.
4. Q20Why is the pouch 3 parathyroid called "inferior" when pouch 3 is above pouch 4?

   The thymus (also pouch 3) migrates caudally and pulls the pouch 3 parathyroid below the pouch 4 parathyroid.
5. Q21What does pouch 5 form, and what does it secrete?

   The ultimobranchial body, which becomes the thyroid C cells that secrete calcitonin.

Key questions

1. Q22What is the only definitive structure formed by a cleft?

   Cleft 1 → external auditory meatus.
2. Q23What happens to clefts 2–4 in normal development?

   Cleft 2 grows caudally over clefts 3–5 and fuses with the epicardial ridge, enclosing the cervical sinus, which is then obliterated.
3. Q24A 6-year-old has a painless lateral neck mass along the anterior border of the SCM. Embryologic failure?

   The cervical sinus persisted because cleft 2 failed to cover and obliterate clefts 3–4 → branchial cleft cyst.

Key questions

1. Q25Which rhombomeres supply neural crest to each arch?

   Arch 1: R1, R2 + midbrain. Arch 2: R4. Arch 3: R6, R7. Arches 4 and 6: R8.
2. Q26How do Hox proteins get into the arches, and what do they set up?

   Neural crest cells carry them in. Hox genes are expressed rostrocaudally, creating a pharyngeal Hox code that gives each arch its identity.
3. Q27What happens in Hoxa-1/Hoxb-1 knockout mice? In Hoxa-3 knockout mice?

   Hoxa-1/Hoxb-1: no ears. Hoxa-3: a DiGeorge-like picture (pouch 3/4 defects).
4. Q28Which factor regulates arch 1, and what does SHH do?

   OTX2 regulates arch 1. SHH regulates Hox genes; SHH knockout mice are headless.
5. Q29If retinoic acid turns Hox genes on, why is too much harmful?

   Hox expression has to stay in a Goldilocks zone. Too much Hox protein disrupts the code as much as too little.
6. Q30How does retinoic acid reach the Hox genes?

   It binds retinoic acid response elements (RAREs) in Hox gene promoters and switches on transcription.

Key questions

1. Q31Why are neural crest cells especially vulnerable to alcohol and retinoic acid?

   They are deficient in superoxide dismutase and catalase, the enzymes that scavenge free radicals.
2. Q32How does alcohol damage neural crest?

   It causes oxidative stress (reactive oxygen species; ↑ F2-isoprostanes), which damages or kills neural crest cells.
3. Q33What are retinoic acid's two mechanisms?

   It generates reactive oxygen species, and it binds RAREs to hyperactivate Hox genes, causing too much Hox protein in neural crest cells.
4. Q34What phenotype did very high retinoic acid produce in mice?

   A Treacher Collins–like phenotype.

Key questions

1. Q35What causes a branchial fistula or lateral cervical cyst?

   Cleft 2 fails to grow caudally over clefts 3–5, so the cervical sinus persists, sometimes with a canal to the skin.
2. Q36What are the features of Treacher Collins, and what goes wrong?

   Malformed zygomatic bones, mandibular hypoplasia, lower-eyelid colobomas and malformed ears. An inherited neural crest defect (Tcof-1) of arches 1 and 2.
3. Q37Which pouches fail in DiGeorge, and what are the findings?

   Pouches 3 and 4: absent thymus and/or parathyroids → immune problems and hypocalcemia, plus abnormal ears and hypertelorism (CATCH-22).
4. Q38Which gene is mutated in Waardenburg syndrome, and what are its features?

   PAX3: cleft palate, deafness, hypertelorism and a white forelock.
5. Q39A newborn has seizures from low calcium and recurrent candidiasis. Which pouches failed?

   Pouches 3 and 4 (no parathyroids, no thymus): DiGeorge syndrome.