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📚 McCarthy's Plastic Surgery

Chapter 46: Embryology of the Head and Neck

Malcolm C. Johnston

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🔑 WHY THIS CHAPTER MATTERS

• Understanding normal development helps explain how craniofacial malformations (cleft lip, palate, cyclopia, etc.) arise.
• Malformations caused experimentally by teratogens in animals mirror those seen in humans, allowing extrapolation.
• Most major craniofacial malformations have already occurred by Day 32 of embryonic development.

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1️⃣ NORMAL DEVELOPMENT: OVERVIEW

📅 Timeline of External Changes (Fig. 46-1)

The figure you uploaded shows 6 stages: Day 19 → Day 22 → Day 25 → Day 32 → Day 44 → Day 50

🔑 Key fact: Surface features up to Day 32 are similar across all higher vertebrates - proving that developmental mechanisms are conserved evolutionarily.

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2️⃣ GASTRULATION & ORGANIZATIONAL PLANS (Fig. 46-2)

What Is Gastrulation?

• After fertilization: cell division → blastocyst (fluid-filled cavity)
• Inner cell mass = the cells that form the actual embryo
• Remaining cells form support structures (e.g., placenta)

The Three Germ Layers

• Epiblast (upper layer)
• Hypoblast (lower layer - forms endoderm)

📌 This migration of epiblast cells through the primitive streak is called "gastrulation"

What Happens Next (Fig. 46-2 F→H)

1. Neural plate thickens and rolls up to form the neural tube
2. Lateral body walls fold under to form the gut
3. Forebrain overgrows the buccopharyngeal membrane and heart
4. As neural folds make contact → neural crest cells migrate away

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3️⃣ KEY CONCEPT: THE ORGANIZER (Mesoderm)

This section is a high-yield conceptual area!

• The mesoderm first induces the overlying ectoderm to differentiate into neural tissue → called "Primary Embryonic Induction"
• The inducing mesoderm is called the "Organizer"
• This induction is an exclusively embryonic event - once the message is delivered, the inducing cells are no longer needed
• The ability of the ectoderm to respond = "Competence"

Mesoderm Organization

1. Notochord (axial)
2. Paraxial mesoderm (alongside notochord)

• A cranial extension of the notochord = Prechordal plate - important for head organization

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4️⃣ EMBRYONIC TISSUES: EPITHELIA vs. MESENCHYME (Fig. 46-3)

The book figure shows a clear diagram of this concept

Two Descriptive Terms:

⚠️ Important: These are histological/descriptive terms - NOT germ layer origin terms. All three germ layers can produce both epithelia and mesenchyme.

Key Mesenchymal Events:

• Mesoderm arranges into compactly arranged somites
• Somites break down to form loosely migrating myoblasts (embryonic muscle cells)

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5️⃣ NEURAL CREST CELLS - THE MOST IMPORTANT CELLS IN HEAD DEVELOPMENT

What Are They?

• Cells that migrate away from the neural folds (just as the neural folds make contact)
• They leave and become dissociated individuals → form loosely arranged mesenchyme
• Cranial crest cells are uniquely powerful - trunk crest cells CANNOT do the same things

What Do Cranial Neural Crest Cells Form?

• Almost ALL skeletal & connective tissue of the face and anterior neck
• Considerable portions of the cranium
• Peripheral nervous system derivatives
• Pigment cells of the skin
• Surround and replace the mesodermal cores of the visceral arches

Migration Pattern (Fig. 46-4)

The book figure shows cranial neural crest cell migration tracked by ³H-thymidine labeling in chick and rat embryos

• Crest cells migrate under the surface ectoderm
• They surround the mesodermal cores of the visceral arches
• After crest cell migration, the initial mesodermal core forms vascular elements
• Endothelial buds invade and vascularize the surrounding crest cell mesenchyme
• After vascularization, the remaining core cells degenerate and are replaced by new mesodermal cells - which become myoblasts (future voluntary/skeletal muscles of the face)

🔑 Treacher Collins syndrome is related to failure of proper ectodermal placode contribution to the peripheral nervous system

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6️⃣ ORGANIZATIONAL PLANS OF ECTODERM AND MESODERM (Fig. 46-5)

The figure shows a detailed diagram of neuromeres, placodes, somites, and visceral arches

Key Points:

• Segmented into neuromeres (labeled 1-9)
• Cranial nerves V (trigeminal), VII (facial), IX (glossopharyngeal), X (vagus) are associated with specific neuromeres

📌 Ganglionic placodes form at some distance from the neural plate and tube; they contribute neurons to cranial sensory ganglia

• In trunk: somites + lateral plate (with kidney region in between)
• In head/anterior neck: only somitomeres (poorly defined, no dermatomes)
• Occipital somites: organized like trunk - have dermatomes, myotomes, sclerotomes

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7️⃣ PRIMARY PALATE & CLEFT LIP FORMATION

Growth Centers (After Neural Crest Migration)

1. Medial nasal prominence
2. Lateral nasal prominence
3. Maxillary prominence

Cleft Lip Mechanism:

• Failure of contact and fusion between the medial and lateral nasal prominences + maxillary prominence → Cleft lip (common and rare forms)
• Morphogenetic movements of these prominences also play a major role

Secondary Palate & Cleft Palate:

• Palatal shelves form from the medial (inner) aspect of the maxillary prominences
• Failure to unite in the midline → Clefts of hard and soft palate

Merging vs. Fusion:

• Distal portions of 1st and 2nd visceral arches unite in the midline by merging (underlying mesenchyme becomes confluent - no epithelial breakdown needed)
• Primary and secondary palate formation requires fusion (breakdown of contracting epithelia IS required)

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8️⃣ HOLOPROSENCEPHALIES & CYCLOPIA

Definition:

• "Holo" = whole; "Prosencephaly" = forebrain (prosencephalon) cavity
• Partial or complete failure of the anterior neural tube to form cerebral hemispheres with ventricles
• Result: only one forebrain cavity in severe cases

Spectrum (Eye Size Decreases as Severity Increases):

1. Mildest - Fetal Alcohol Syndrome (subtle midline facial deficiency)
2. Moderate forms
3. Cyclopia Perfecta - One large median eye (this is NOT on the spectrum - it's too extreme)

Cause:

• Deficiency of the medial portion of the anterior neural plate
• This leads to more closely approximated olfactory placodes → small medial nasal prominences → small midface
• Most can be induced by ethanol in experimental animals

Fetal Alcohol Syndrome (FAS) (Fig. 46-6)

The figure shows two children with FAS (A, B) alongside FAS and control mouse embryos (C, D)

• Narrow forehead
• Short palpebral fissures
• Small nose
• Small midface
• Long upper lip with deficient philtrum

• Ethanol administration → cell death in the medial anterior neural plate
• Ethanol (given at gastrulation) → midface defects
• Mesoderm was severely reduced in ethanol-treated embryos

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9️⃣ VASCULAR DEVELOPMENT (mentioned briefly)

• Lateral plate mesoderm in the head = primarily angiogenic
• The cores of visceral arches form vascular elements
• Endothelial buds invade crest cell mesenchyme to vascularize the face

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🔟 EMBRYO FOLDING (TUBULATION) & NEURAL TUBE DEFECTS (Fig. 46-2, 46-7, 46-8, 46-9)

Folding Movements Form TWO Tubes:

1. Neural tube (brain and spinal cord)
2. Gastrointestinal tube (endodermally lined gut)

Neural Tube Closure Mechanism:

• Involves coordinated contraction of filamentous actin-myosin meshwork = "terminal web" just beneath the luminal lining cell surfaces
• Terminal webs are involved in many epithelial foldings, including morphogenetic movements of the olfactory placode

Neural Tube Defects (NTDs):

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1️⃣1️⃣ OTOCEPHALY (Fig. 46-8)

The figure shows two drawings of otocephalic infants (A = milder, B = severe)

What is Otocephaly?

• Literally: "ear head" (German: Otozephalie)
• A spectrum of malformations caused by breakdown of mesodermal cores in the first visceral arch

Spectrum:

Cause:

• Failure of vascularization from the mesodermal core → neural crest cells appear normal but failure of vascularization leads to complete arch breakdown
• Mesodermal core cells normally break down after vascularization of the neural crest cell mesenchyme

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1️⃣2️⃣ KEY FIGURE SUMMARIES

Fig. 46-1 (you uploaded)

Fig. 46-2 (you uploaded)

• ps = primitive streak
• nc = neural crest
• n = notochord
• lp = lateral plate
• s = somites
• ep = epiblast
• hy = hypoblast

Fig. 46-3 (you uploaded)

Fig. 46-4 (you uploaded)

Fig. 46-5 (you uploaded)

• A: Lateral view of embryo with labeled structures (bp=buccal plate, p=anterior pituitary anlage, op=olfactory placode, ef=eye field, pp=prechordal plate, n=notochord, nc=neural crest)
• B: Cross-section showing ectoderm-mesoderm-endoderm layers with placode contact
• C: Neuromere segmentation with cranial nerve associations (V, VII, IX, X)
• D: Post-tubulation cross-section showing somite, ganglion, placode, neural crest, notochord

Fig. 46-6 (you uploaded)

Fig. 46-7 (you uploaded)

• A = Schematic of human embryo showing nasal (na), lens (l), otic (o) placodes, heart (h), buccopharyngeal membrane (b), eye field (e), notochord (n), prechordal plate (pp), primitive streak (ps)
• B = Same in ethanol-treated embryo (nasal placodes too close to midline → FAS-like malformation)
• C-E = Scanning electron micrographs of mouse embryos showing normal placode development

Fig. 46-8 (you uploaded)

• A = Milder form (agnathia): mandible and other 1st arch derivatives absent
• B = Severe form: only external ears remain - hence "ear head" (otocephaly)

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🎯 HIGH-YIELD QUICK RECAP

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📝 EXAM TIPS

1. Mesenchyme vs. Epithelium - don't confuse these descriptive terms with germ layer origins
2. Neural crest cells are the star of head/neck development - they are essentially displaced trunk mesoderm equivalents in the head
3. Placodes are ectodermal thickenings outside the neural plate; important for cranial nerve ganglia and sense organs
4. Treacher Collins = placode/peripheral nervous system issue
5. The concept of "growth centers" after crest cell migration dominates primary palate formation
6. The prechordal plate is not notochord but has similar organizing ability - its failure contributes to cyclopia and holoprosencephaly
7. FAS mimics holoprosencephaly spectrum at the mild end

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