Lecture 13: Development of the Ear and Eye, and related birth defects

What are the 3 divisions of the ear, and what does each do?

External ear = collects sound; Middle ear = conducts sound from external to internal ear; Internal ear = converts sound waves to nerve impulses (cochlea) and registers equilibrium changes (semicircular canals, vestibule)

What makes up the vestibule of the internal ear?

Utricle + saccule

When do otic placodes appear?

~22 days

What does the otic placode invaginate to become?

The otic vesicle (= auditory vesicle = otocyst)

What does the otic vesicle (otocyst) give rise to?

Almost the entire inner ear

What germ layer/structure induces the otic placode to form?

The invaginating neural tube (rhombencephalon) induces the adjacent surface ectoderm to form the otic placode

List the ear developmental sequence with ages: otic placode → otic pit → otic vesicle

Otic placode (22 days) → Otic pit (27 days) → Otic vesicle (4.5 weeks)

The otocyst divides into what two components?

(1) Ventral component: saccule and cochlear duct; (2) Dorsal component: utricle, semicircular canals, and endolymphatic duct

Which otocyst-derived structures come from the VENTRAL component?

Saccule and cochlear duct

Which otocyst-derived structures come from the DORSAL component?

Utricle, semicircular canals, and endolymphatic duct

What does the cochlear duct develop into?

The Organ of Corti (hair cells covered by the tectorial membrane)

What are inner hair cells of the Organ of Corti also known as?

The auditory sensory neurons

What does the utricle give rise to?

The semicircular canals

Where is the spiral ganglion located, and what does it contain?

Inside the cochlea; contains inner hair cells (auditory sensory neurons)

What are the embryonic origins of the spiral ganglion's cells?

Inner hair cells (neurons) from the otic placode/otocyst; glia from neural crest

What is another name for the vestibular ganglia?

Scarpa's ganglion

Where are the vestibular ganglia located, and what do they contain?

Outside the labyrinth; contain vestibular hair cells (vestibular sensory neurons)

What are the embryonic origins of the vestibular ganglia's cells?

Vestibular hair cells (neurons) from otic placode/otocyst; glia from neural crest

What pharyngeal structure gives rise to the tympanic cavity and auditory (Eustachian) tube?

The 1st pharyngeal pouch (both structures)

What is the embryonic origin of the ear ossicles?

Neural crest-derived mesenchyme

Which pharyngeal arch gives rise to the malleus and incus?

1st pharyngeal arch

Which pharyngeal arch gives rise to the stapes?

2nd pharyngeal arch

What gives rise to the external auditory meatus?

The 1st pharyngeal cleft

What are the 3 tissue layers of the eardrum (tympanic membrane) and their origins?

(1) Ectoderm lining at the bottom of the auditory meatus; (2) Endoderm epithelial lining of the tympanic cavity; (3) Connective tissue layer from mesoderm

What are auricular hillocks, and what do they form?

Six mesenchymal proliferations at the dorsal ends of the 1st and 2nd pharyngeal arches, surrounding the 1st pharyngeal cleft; they form the auricle (pinna)

How common is congenital hearing loss?

1–3 in 1,000 births

What are the 3 types of congenital hearing loss?

Conductive, sensorineural, and mixed

What causes conductive hearing loss, and where are the defects?

Defects in the outer ear or middle ear

What causes sensorineural hearing loss, and where are the defects?

Defects in the inner ear or the neural pathway to/inside the brain; this is the MOST COMMON type

What is Michel's aplasia?

Total labyrinthine aplasia — complete lack of development of the entire inner ear, due to early arrest of otic placode differentiation at the 3rd week of gestation

What is cochlear aplasia?

Complete absence of the cochlea, with the semicircular canals and vestibule present; due to arrest of inner ear development at the 3rd–6th week of gestation

What is Mondini malformation (dysplasia)?

The cochlea makes spiral turns incompletely, due to arrest of cochlear development at the 7th week of gestation

Rank the inner ear malformations by how early the developmental arrest occurs (earliest to latest)

Michel's aplasia (3rd week) → Cochlear aplasia (3rd–6th week) → Mondini malformation (7th week)

What is microtia?

A structural birth defect of the external ear (auricle) involving an abnormally small or underdeveloped ear

What are preauricular appendages?

Skin tags near the ear (external ear malformation)

What are preauricular pits?

Shallow depressions near the ear (external ear malformation)

Spot the Swap: "The otic vesicle invaginates to become the otic placode." True or False — what's wrong?

False — reversed. The otic PLACODE invaginates to become the otic VESICLE (otocyst)

Spot the Swap: "The malleus and incus arise from the 2nd pharyngeal arch, and the stapes from the 1st." True or False — what's wrong?

False — reversed. Malleus and incus = 1st arch; stapes = 2nd arch

Spot the Swap: "In Michel's aplasia, the semicircular canals and vestibule are present but the cochlea is absent." True or False — what's wrong?

False — this describes COCHLEAR aplasia. Michel's aplasia is total absence of the ENTIRE inner ear

What embryonic structure gives rise to the optic vesicle?

The diencephalon, via the optic groove (Diencephalon → Optic groove → Optic vesicle)

What does the optic vesicle induce, and in what tissue?

It induces the surface ectoderm to form the lens placode

What does the optic vesicle become next?

The optic cup

How is the choroid fissure formed, and what is its function?

Formed by invagination of the inferior surface of the optic cup; it allows the hyaloid artery to reach the inner chamber of the eye

When do the lips of the choroid fissure fuse?

During the 7th week

What happens to the lens placode after the optic cup forms?

The lens placode invaginates to become the lens vesicle, then loses contact with the surface ectoderm

What does the retina arise from, and what are its two layers?

Almost entirely from the optic cup: pigmented layer of the retina, and neural layer of the retina (photoreceptor cells, bipolar cells, ganglion cells)

What is the embryonic origin of the iris?

Mostly the tip of the optic cup, including the smooth muscles (sphincter pupillae, dilator pupillae)

What is the embryonic origin of the ciliary body?

Optic cup (ciliary process) and neural crest cells (ciliary muscle)

What is the embryonic origin of the lens, and describe its formation

Entirely from the lens vesicle; posterior wall cells elongate into primary lens fibers that fill the lumen, reaching the anterior wall by the end of the 7th week

What is the embryonic origin of the cornea?

Surface ectoderm (corneal epithelium) and neural crest (corneal stroma, corneal endothelium)

What is peri-ocular mesenchyme (POM), and when does it surround the eye?

Loose mesenchyme (mostly neural crest, some mesoderm) that completely surrounds the eye by the end of the 5th week

What does the inner layer of peri-ocular mesenchyme become, and from what tissue?

The choroid (blood vessels), mostly from mesoderm

What does the outer layer of peri-ocular mesenchyme become, and from what tissue?

The sclera, from neural crest

Where do the neural crest cells that form peri-ocular mesenchyme mostly originate?

The forebrain and midbrain

List eye structures with MAJOR neural crest contribution

Sclera, cornea, ciliary body

List eye structures with MINOR neural crest contribution

Iris, choroid, retina

Which eye structure receives NO contribution from neural crest?

The lens (entirely from lens placode/surface ectoderm)

How do neural crest cells regulate optic cup and lens placode development?

Indirectly, through secreted signaling molecules

Spot the Swap: "The lens is derived largely from neural crest, while the cornea receives no neural crest contribution." True or False — what's wrong?

False — reversed. The lens has NO neural crest contribution; the cornea's stroma and endothelium ARE from neural crest

Spot the Swap: "The choroid's outer layer comes from neural crest and the sclera's origin is mostly mesoderm." True or False — what's wrong?

False — reversed. Choroid (inner layer) = mostly mesoderm (vessels); Sclera (outer layer) = neural crest

What is cyclopia, and what causes it?

A single central eye/eye field, seen in cases of alobar holoprosencephaly; caused by perturbation of SHH (Sonic Hedgehog) signaling

What is anophthalmia?

A missing eye

What is microphthalmia?

An abnormally small eye

What is a coloboma?

A gap in one of the structures of the eye, such as the iris, retina, choroid, or eyelid

How common is coloboma?

~1 in 2,000 births

What is the most common type of coloboma, and what causes it?

Coloboma of the iris, due to failure of choroid fissure fusion

What are the possible clinical presentations of coloboma?

Can be asymptomatic, or can cause blurred vision

Spot the Swap: "Coloboma most commonly affects the lens, caused by failure of the optic groove to close." True or False — what's wrong?

False — coloboma most commonly affects the IRIS, caused by failure of the CHOROID FISSURE to fuse