HNSS18 · 3 learning objectives

Embryology of the Eye & Ear

LO 1

Describe the embryologic origins of the major structures of the eye and ear

Key questions

Q1What do the inner and outer layers of the optic cup form?
Inner layer: neural retina. Outer layer: retinal pigment epithelium.
Q2Which eye structures come from surface ectoderm?
The lens and the corneal epithelium.
Q3Which eye structures come from neural crest?
Corneal stroma and endothelium, iris stroma, and the ciliary muscle and stroma.
Q4Which eye muscles come from neuroectoderm rather than mesoderm?
The sphincter and dilator pupillae (from the anterior optic cup).
Q5What are the origins of the inner, middle and external ear?
Inner: otic placode (surface ectoderm). Middle: pouch 1 + arches 1 and 2. External: cleft 1 + arches 1 and 2.
Q6Which structure is built from pouch 1, cleft 1 and the mesenchyme between them?
The tympanic membrane.
Q7Where does the bony labyrinth come from, vs the membranous labyrinth?
Bony: mesenchyme around the otic vesicle forms a cartilaginous capsule that ossifies. Membranous: the otic vesicle itself.

Eye: neuroectoderm (optic cup) makes retina, RPE, iris/ciliary epithelium and iris muscles; surface ectoderm makes lens and corneal epithelium; neural crest makes the stroma. Ear: inner = otic placode; middle = pouch 1 + arches 1–2; external = cleft 1 + arches 1–2.

Eye

Structure	Origin
Neural retina	Inner layer of optic cup (neuroectoderm)
Retinal pigment epithelium	Outer layer of optic cup
Optic nerve	Optic stalk + retinal ganglion cell axons
Lens	Surface ectoderm (lens placode)
Corneal epithelium	Surface ectoderm
Corneal stroma + endothelium	Neural crest
Iris epithelium + sphincter/dilator pupillae	Anterior optic cup (neuroectoderm)
Iris stroma	Neural crest
Ciliary epithelium	Optic cup
Ciliary muscle + stroma	Neural crest mesenchyme
Hyaloid artery	Runs in the choroid fissure

Ear

Structure	Origin
Membranous labyrinth	Otic placode (surface ectoderm) → otic vesicle
Bony labyrinth	Mesenchyme around the otic vesicle → cartilaginous capsule → ossifies
CN VIII ganglia	Neuroblasts from otic epithelium
Tympanic cavity + auditory tube	Pouch 1 (tubotympanic recess)
Malleus + incus	Arch 1 (Meckel's)
Stapes	Arch 2 (Reichert's)
Tympanic membrane	Pouch 1 + cleft 1 + mesenchyme between
External auditory meatus	Cleft 1
Auricle	6 auricular hillocks: 1–3 arch 1, 4–6 arch 2. Hillock 1 → tragus; hillock 6 → antitragus. The lobule is not from hillocks. Pinna = elastic cartilage

HY · Step 1

Sphincter and dilator pupillae come from neuroectoderm, the classic exception to "muscles come from mesoderm."
The tympanic membrane is the one structure with all three germ layers: ectoderm (cleft 1), mesoderm (middle), endoderm (pouch 1).
Hyaloid artery → its proximal part persists as the central retinal artery.

LO 2

Explain the major developmental steps in the formation of the eye and the inner, middle, and external ear

Key questions

Q8Where do the eyes begin, and which gene marks the eye fields?
In the anterior neural plate (prosencephalon/diencephalon); the eye fields express PAX6.
Q9What induces the lens placode, and what are the steps that follow?
The optic vesicle induces surface ectoderm. Lens placode → lens pit → lens vesicle, which pinches off; meanwhile the optic vesicle invaginates into the optic cup.
Q10What does the lens vesicle induce next?
Corneal development.
Q11What runs through the choroid fissure?
The hyaloid artery.
Q12When do the eyelids fuse, and when do they reopen?
They fuse at the start of the second trimester and reopen at the start of the third.
Q13What is the sequence for the inner ear, and where is the otic pit?
Otic placode → otic pit (dorsal to cleft 2) → otic vesicle, which pinches off from the surface.
Q14Where do the CN VIII ganglia come from?
Neuroblasts delaminate from the otic epithelium to form the statoacoustic ganglion, which splits into the vestibular and spiral ganglia.
Q15What do the utricular and saccular portions of the otic vesicle form?
Utricular: utricle + semicircular ducts. Saccular: saccule + cochlear duct (→ Organ of Corti).
Q16How does the auricle form, and why do the ears move up?
From 6 auricular hillocks (1–3 arch 1, 4–6 arch 2). The ears start caudal to the jaw, and jaw growth shifts them up and vertical.
Q17What is the meatal plug, and when does it clear?
An epithelial plug filling the external canal. It breaks down around month 7, opening the canal to the eardrum.

Eye: the optic vesicle induces the lens placode, and each shapes the other into optic cup + lens vesicle. Inner ear: otic placode → pit → vesicle, which splits into utricular and saccular parts.

Eye

Approx. age	Step
~Day 17	Eye fields in anterior neural plate (prosencephalon), PAX6-expressing
~Day 21–24	Forebrain grows forward; eye field cells invaginate → optic grooves
~Day 25–28	Optic grooves → optic vesicles + optic stalks
~Day 28–33	Optic vesicle contacts surface ectoderm → induces lens placode (thickening)
~Day 36	Reciprocal induction: optic vesicle invaginates → bilayered optic cup; lens placode → lens pit → lens vesicle pinches off. Lens vesicle then induces the cornea
~Wk 6	Invagination creates the choroid fissure inferiorly; hyaloid artery runs through it. Fissure then closes
~Wk 7	Posterior lens fibers elongate and fill the lens cavity; lens grows at its equator (PAX6, SOX2, MAF). Cornea differentiates. Neural retina thickens, pigmented layer thins
~Wk 7–8	Anterior chamber forms; pupillary membrane normally regresses before birth
~Wk 8–9	Iris grows from anterior rim of optic cup; eyelids begin forming at the end of the embryonic period
~Wk 10 → 3rd tri	Eyelids fuse (start of 2nd trimester) and reopen (start of 3rd trimester)
~Wk 15	Two optic-cup layers fold → ciliary processes

Optic vesicleinduces →lens placode→lens pit→lens vesicleinduces →cornea

Ear

Inner

~Day 22: otic placode (surface ectoderm)
~Day 26–28: otic pit, dorsal to cleft 2
~Day 29: otic vesicle pinches off
Surrounding mesenchyme → cartilaginous capsule → bony labyrinth; the otic vesicle itself becomes the membranous labyrinth
~Day 30: neuroblasts delaminate → statoacoustic ganglion → vestibular + spiral ganglia (CN VIII)
~Day 36: vesicle divides
- Dorsal → endolymphatic duct + sac
- Utricular → utricle + semicircular ducts
- Saccular → saccule + cochlear duct (~wk 9) → Organ of Corti

Middle

Pouch 1 → tubotympanic recess → tympanic cavity + auditory tube
Arch 1 → malleus, incus; arch 2 → stapes
The recess keeps expanding late in gestation until the tympanic cavity surrounds the ossicles

External

Wk 5–6: 6 auricular hillocks around cleft 1
Ears start caudal to the lower jaw; jaw growth moves them up and vertical
Cleft 1 → external auditory meatus
A meatal plug of epithelial cells fills the canal, then breaks down around month 7, opening the canal to the tympanic membrane

Memory hook

Utricle → semicircular (rotation + linear); Saccule → Sound (cochlear duct).

LO 3

Recognize selected developmental abnormalities and explain their embryologic basis

Key questions

Q18What causes cyclopia?
Loss of SHH from the ventral midline, so PAX6 isn't repressed there and the two eye fields merge.
Q19A child has a keyhole-shaped defect at the bottom of the iris. What failed to happen?
The choroid fissure failed to close → coloboma.
Q20What does a persistent pupillary membrane risk?
If it blocks the visual axis, deprivation amblyopia.
Q21Which first-trimester drugs are linked to external ear anomalies?
Streptomycin, salicylates and thalidomide.
Q22Which genes are linked to hair-cell loss, and what does each affect?
POU4F3: hair cell degeneration. Connexin 26: supporting-cell gap junctions. c-Kit: stria vascularis.
Q23Why can ears end up low-set?
Abnormal auricular hillock (arch 1/2) development, or failure of jaw growth to shift the ears upward. Often a marker of an arch or chromosomal syndrome.

The lecture's three: cyclopia (no SHH → eye fields don't separate), coloboma (choroid fissure doesn't close), persistent pupillary membrane (fails to regress).

Abnormality	Embryologic basis	Consequence
Cyclopia	No SHH from the ventral midline → PAX6 isn't repressed in the midline → the two eye fields converge	Single midline eye; forebrain deficient
Coloboma	Choroid fissure fails to close	Inferior "keyhole" gap in iris (can affect retina, choroid, optic nerve)
Persistent pupillary membrane	Pupillary membrane fails to regress before birth	Strands across the pupil. If it blocks the visual axis → deprivation amblyopia
Drug-induced ear anomalies	External ear is very sensitive to first-trimester drug exposure (streptomycin, salicylates, thalidomide)	Pharyngeal and external ear malformations
Waardenburg syndrome	Autosomal dominant; neural crest (PAX3) defect affecting pigment cells	Congenital deafness + pigment abnormalities (white forelock)
Genetic hair-cell loss	POU4F3 (hair cell degeneration), connexin 26 (supporting-cell gap junctions), c-Kit (stria vascularis)	Sensorineural hearing loss
Low-set / malformed ears	Auricular hillocks (arches 1–2) or failed upward shift with jaw growth	Marker of arch or chromosomal syndromes

HY · Step 1 add-ons (not in lecture)

Cyclopia sits on the holoprosencephaly spectrum (SHH mutation, trisomy 13, maternal diabetes, alcohol).
Aniridia = PAX6 mutation; part of WAGR (Wilms tumor, Aniridia, GU anomalies, intellectual disability, 11p13).
Congenital rubella: cataracts, sensorineural deafness, PDA. Congenital CMV: most common infectious cause of hearing loss.
Lower-eyelid coloboma is a separate thing: it's a Treacher Collins sign (arch 1 NC), not a choroid fissure defect.

Extra

Ear structure, histology and pathology

Key questions

Q24Which fluid fills the membranous labyrinth, and what is its key ion?
Endolymph, high in K⁺ (made by the stria vascularis). Perilymph, between the membranous and bony labyrinths, is high in Na⁺.
Q25Which cochlear compartment holds the Organ of Corti?
The scala media (cochlear duct), filled with endolymph.
Q26Inner vs outer hair cells: which transmits and which amplifies?
Inner hair cells transmit to the spiral ganglion; outer hair cells amplify.
Q27Maculae vs cristae ampullares: what does each sense?
Maculae (utricle, saccule): linear acceleration and gravity, using otoliths. Cristae (semicircular canals): rotation, using the cupula.
Q28What does each middle-ear muscle dampen?
Stapedius (VII): loud sounds. Tensor tympani (V3): the sound of chewing.
Q29Where is the cone of light in each ear?
5 o'clock in the right ear, 7 o'clock in the left.
Q30Which disease fixes the stapes, and what kind of hearing loss results?
Otosclerosis; conductive hearing loss.
Q31What causes Ménière disease vs BPPV?
Ménière: excess endolymph (hydrops). BPPV: otoliths dislodged into a semicircular canal.

This material was covered in last year's version of this lecture (Embryology & Histology of the Ear) but isn't part of this year's lecture. Treat it as lower priority for this lecture. Ear histology is also covered in the Histology of the Eye & Ear lecture.

The inner ear has two fluids: endolymph inside the membranous labyrinth (high K⁺) and perilymph between the membranous and bony labyrinths (high Na⁺). Hair cells bend → channels open → K⁺ enters → depolarization → CN VIII.

Cochlea (hearing)

Scala vestibuli: perilymph
Scala media (cochlear duct): endolymph, made by the stria vascularis; holds the Organ of Corti
Scala tympani: perilymph
Organ of Corti: rows of hair cells (1 inner, 3 outer) with stereocilia in the tectorial membrane. Inner hair cells send the signal to the spiral ganglion; outer hair cells amplify it

Vestibular (balance)

Maculae of utricle and saccule: linear acceleration and gravity. Stereocilia sit in an otolithic membrane loaded with otoliths (calcium carbonate)
Cristae ampullares in the semicircular canal ampullae: rotation. Hair cells project into the cupula; endolymph lags behind during head turns and pushes on it
Bending toward the kinocilium → tip links open channels → K⁺ enters → depolarization → Ca²⁺ entry → neurotransmitter → CN VIII

External auditory meatus→tympanic membrane→malleus → incus → stapes→oval window→scala vestibuli→scala media (hair cells, by frequency)→scala tympani→round window

Middle ear

Stapedius (CN VII): smallest muscle in the body; dampens loud sound
Tensor tympani (V3): dampens the sound of chewing
Eustachian tube: middle ear to nasopharynx; equalizes pressure across the eardrum
Chorda tympani (VII) passes between the malleus and incus → taste, anterior 2/3 of tongue. CN VII compression in the middle ear → facial palsy ± taste loss

External ear and eardrum

Pinna: elastic cartilage + connective tissue
Canal: hair follicles, sebaceous glands (sebum), ceruminous glands (cerumen/wax)
Tympanic membrane: small pars flaccida at the top, larger pars tensa below (most perforations)
Handle of the malleus attaches centrally; the umbo makes the cone of light: 5 o'clock in the right ear, 7 o'clock in the left

Disease	Region	Mechanism / presentation	Treatment
Ménière disease	Inner	↑ Endolymph (endolymphatic hydrops) → membranes rupture and fluids mix → episodic vertigo, nausea, tinnitus, hearing loss	Low-salt diet, diuretics, physical therapy, labyrinthectomy
BPPV	Inner	Otoliths from the utricle/saccule slip into a semicircular canal → brief vertigo after head movement	Canalith repositioning (head maneuvers)
Hair-cell loss	Cochlea	Genetic (POU4F3, connexin 26, c-Kit), stereocilia bundle defects, loud noise	Hearing aids; cochlear implant (needs an intact auditory nerve)
Otitis media	Middle	Bacteria climb the eustachian tube from the nasopharynx	Antibiotics
Cholesteatoma	Middle	Squamous epithelium ("skin") grows through the eardrum into the middle ear; can erode bone	Surgical removal
Otosclerosis	Middle	Bony overgrowth fixes the stapes → conductive hearing loss; hereditary or hormonal (after pregnancy)	Stapedectomy with prosthesis (~9/10 restore hearing)
Auricular hematoma ("wrestler's ear")	External	Blunt trauma → blood under the perichondrium → cartilage overgrowth	Drain early (deformity likely after ~7 days)
Perichondritis / chondritis	External	Usually bacterial infection of perichondrium and cartilage	Antibiotics
Exostoses ("surfer's ear")	External	Dense bony growths in the canal from repeated cold water	Usually none, unless the canal is blocked
Cerumen impaction	External	Wax builds up; can block the canal and raise infection risk	Avoid pushing it deeper
Otitis externa	External	Outer ear infection; can perforate the eardrum	Depends on cause

HY · Step 1

Conductive loss (otosclerosis, otitis media, cerumen): Weber lateralizes to the bad ear; bone > air (Rinne abnormal). Sensorineural loss (hair cells, Ménière): Weber lateralizes away; air > bone.
Ménière triad: episodic vertigo + tinnitus + sensorineural hearing loss (with ear fullness).
Cholesteatoma: keratin-filled squamous debris behind the eardrum; painless otorrhea, conductive loss.
Ototoxic drugs: aminoglycosides (streptomycin, gentamicin), cisplatin, loop diuretics, high-dose salicylates.

Application questions

1. A mutation abolishes signaling from the optic vesicle to the overlying ectoderm. Which structure fails to form first?

Neural retina
Lens
Retinal pigment epithelium
Optic stalk

Answer

B. The optic vesicle induces surface ectoderm to form the lens placode. Without the lens vesicle, the cornea is affected next.

2. Which structure forms from the same embryonic tissue as the neural retina?

Corneal stroma
Lens fibers
Sphincter pupillae muscle
Ciliary muscle

Answer

C. Sphincter and dilator pupillae come from the anterior optic cup (neuroectoderm), like the retina. Corneal stroma and ciliary muscle are neural crest; lens is surface ectoderm.

Each objective opens with the one-line answer. Yellow boxes are high-yield Step 1 add-ons and may go beyond the lecture.