UNSW Embryology

Development of the Organs of Audition and Equilibrium

Outer Ear

© Dr Mark Hill (2008)

Acknowledgements

Introduction

Hearing Anatomy	External Ear (Auricula or Pinna)

The external ear is derived from 6 surface hillocks (auricular hillocks), three on each of pharyngeal arch 1 and 2.

The external auditory meatus is derived from the 1st pharyngeal cleft.

Page Links: Introduction | stage 13/14 embryo | stage 22 embryo | Development Timing | Auricular Hillocks Adult Ear Growth | Abnormalities | Development Overview | References | Glossary

External Link: Embryo Images Unit - External Ear

Some Recent Findings

Ishimoto S, Ito K, Karino S, Takegoshi H, Kaga K, Yamasoba T. Hearing levels in patients with microtia: correlation with temporal bone malformation. Laryngoscope. 2007 Mar;117(3):461-5.

"The hearing level in microtic ears correlated with the formation of oval/round windows and ossicular development but not with the degree of middle ear aeration, facial nerve aberration, or severity of microtia."

Meijerman L, van der Lugt C, Maat GJ. Cross-sectional anthropometric study of the external ear. J Forensic Sci. 2007 Mar;52(2):286-93.

"The effect of age on auricle length, earlobe length, and auricle width was explored using univariate analyses of variance. ...Regression coefficients of age corrected for stature were assumed to be less accurate. Antihelix prominence and helix width were analyzed using data of 175 subjects, and appeared unaffected by age. As lobe expansion appeared to exceed the estimated cartilage expansion, it was assumed that particularly the imprint of the lobe would be less stable with time."

(More? Adult Ear Growth)

Edston E. The earlobe crease, coronary artery disease, and sudden cardiac death: an autopsy study of 520 individuals. Am J Forensic Med Pathol. 2006 Jun;27(2):129-33.

"...previous studies have demonstrated a correlation between diagonal earlobe creases (ELC) and coronary artery disease (CAD). ...It is concluded that in a patient population similar to that in the present study the ELC sign could be especially useful in screening for premature CAD in younger individuals."

Search PubMed: external ear development | Pinna development |

Stage 13/14 Embryo

A2: Otocyst (R). Apex of otocyst (primordium of L endolymphatic sac).	A3: Otocyst; surrounding mesenchyme = otic capsule. Note proximity of otocyst to wall of rhombencephalon. Superior glossopharyngeal ganglion. Vestibulo-cochlear-facial ganglion complex (R). Trigeminal ganglion (not in image excerpt).	A4: Indentation in rostral margin of otocyst = primordium of utriculosaccular canal. Note alignment of superior cardinal vein (LS) in relation to the nerve trunks (XS). Trigeminal ganglion (not in image excerpt). Note variation in height of cells of L otocyst wall. Dorsal end of 1st pharyngeal arch and groove (not in image excerpt).	A5: Facial ganglion (R). "Floor" of L otocyst. Note on R, the former position of the otocyst in relation to the 2nd pharyngeal arch.

Stage 22 Embryo

B4: Cochlear duct and temporal cartilage. Semicircular duct (ampulla on L). precartilage of auricle (pinna). malleus (medial, L). Incus (lateral, L).

B5: Extemal auditory meatus. Auricle. Incus (dorsal). Malleus (ventral). Tubotympanic recess (auditory rube). Tensor tympani m. (L). Utricle. Semicircular ducts. Intemal auditory meatus (R), containing vestibular and spiral ganglia. Endolymphatic sac (L). Note proximity of sac to choroid plexus of 4th ventricle.

B6: External auditory meatus. Primordium of tympanic membrane (L). Manubrium of malleus(L). Basal turn of cochlea duct (L). Endolymphatic sac (R). Common crus (R). Junction of utricle and saccule (R). Meckel's cartilage. Stapes (R). Auditory tube.

Historic Images

Left External Ear (Auricula or Pinna)	Cartilage of right auricula (Cranial surface)

Development Timing

Week 3 - otic placode, otic vesicle

Week 5 - cochlear part of otic vesicle elongates (humans 2.5 turns)

Week 9 - Mesenchyme surrounding membranous labrynth (otic capsule) chondrifies

Week 12-16 - Capsule adjacent to membranous labrynth undegoes vacuolization to form a cavity (perilymphatic space) around membranous labrynth and fills with perilymph

Week 16-24 - Centres of ossification appear in remaining cartilage of otic capsule form petrous portion of temporal bone. Continues to ossify to form mastoid process of temporal bone.

3rd Trimester - Vibration acoustically of maternal abdominal wall induces startle respone in fetus.

(These are Human embryonic timings, not clinical which is based on last menstral period +2 weeks)

3 Sources:

Inner ear - epidermal otic placode at level of hindbrain.

Middle ear - cavity: 1st pharyngeal pouch, ossicles: mesenchyme 1st and 2nd pharyngeal arches.

Outer ear - external auditory meatus: 1st pharyngeal cleft, auricle: 6 hillocks 1st and 2nd pharyngeal arches.

Auricular Hillocks

Adult Ear Growth

During adult life the external ears continue to grow in size, a recent paper has analysed the rate of adult male and female growth of auricle length, earlobe length, and auricle width in mm/yr. Growth of male auricle and earlobe length was greater than female and other parameters (antihelix prominence, helix width) were unaffected by age.

Growth (mm/yr)	auricle length	earlobe length	auricle width
Males	0.178	0.115	0.073
Females	0.162	0.100	0.073

(Data from: Meijerman L, van der Lugt C, Maat GJ. Cross-sectional anthropometric study of the external ear. J Forensic Sci. 2007 Mar;52(2):286-93.)

Outer Ear Abnormalities

Microtia | Preauricular Sinus | Preauricular Tag | External Meatus Stenosis |

Microtia

The condition in humans of an abnormally small external ear is called Microtia. This is generally surgically repaired by use of rib cartilage to reconstruct the external ear. A recent study has identified a mouse model for this condition with the knockout of the Pact gene.

Newborn Microtia (Image: NZ National Women's Health Ear Anomalies)

OMIM Database Search: "Microtia" (2006 - 25 search results)

Search PubMed May 2006 "Microtia" 449 reference articles of which 37 were reviews.

Search PubMed: Microtia | external ear defects

References

Rowe TM, Rizzi M, Hirose K, Peters GA, Sen GC. A role of the double-stranded RNA-binding protein PACT in mouse ear development and hearing. Proc Natl Acad Sci U S A. 2006 Mar 29 ".. Pact(-/-) mouse were reduced size and severe microtia. As a result of the congenital abnormality of both outer and middle ears, these mice were hearing impaired. Our study demonstrated an essential role of PACT in mammalian ear development and produced the first animal model for studying human microtia."

Zim SA. Microtia reconstruction: an update. Curr Opin Otolaryngol Head Neck Surg. 2003 Aug;11(4):275-81. Review. "...autogenous rib cartilage continues to be the gold standard for microtia repair. Numerous refinements and modifications in the original technique described by Tanzer have paved the way for exceptional results in experienced hands. However, ideal results are not always achieved, and there continue to be drawbacks with the standard approach to reconstruction with autogenous rib cartilage. In an attempt to circumvent these shortcomings, surgeons have developed alternative or adjuvant techniques to repair the microtic ear, including the use of tissue expansion, alloplastic implants, and osseointegrated prostheses. Finally, greater emphasis is being placed on early atresia repair in appropriate candidates."

Preauricular Sinus

Preauricular sinus in ascending limb of the helix

Preauricular sinus occurs in 0.25% births, is bilateral (hereditary) in 25-50% of cases and unilateral (mainly the left). They are developmental and generally occur on the surface in anterior margin of the ascending limb of the helix, and the duct runs inward to the perichondrium of the auricular cartilage and in some cases extend into the parotid gland. Postnatally they are a site for infection.

Search PubMed: Preauricular Sinus

Links: Medline Plus - Preauricular tag or pit

Preauricular Tag

Skin tags in front of the external ear opening are common in neonates and in most cases are normal, though in some cases are indicative of other associated abnormalities.

Search PubMed: Preauricular Tag

Links: Medline Plus - Preauricular tag or pit

External Meatus Stenosis

Stenosis of the external meatus

Search PubMed: external meatus stenosis

Developmental Overview

Development of Hearing - 3 divisions of ear

• outer
  • external auditory meatus (ear canal)
  • functions to collect sound and gude it to the tympanic membrane
• middle
  • tympanic cavity
  • functions to convert sound pressure waves into mechanical waves of typanic membrane
  • ossicles reduce amplitude but increase force to drive fluid-filled inner ear
  • eustacian tube allows equalization of pressure (into oral cavity)
• inner
  • duct system
  • functions to convert hair displacement into neural signals
  • cochlear (sound)
  • semicircular canals (balance)
  • vestibulocochlear nerve
  • Organ of Corti
  • Hair Cells

Pinna- Auricle

• develops from six aural hillocks
• 3 on first arch
• 3 on second arch
• originally on neck, moves cranially during mandible development

Outer- external auditory meatus

• derived from first pharyngeal cleft
• ectodermal diverticulum
• week 5
• extends inwards to pharynx
• until week 18 has ectodermal plug
• plug forms stratified squamous epithelia of canal and outer eardrum
• Outer Ear Genes
  • controlled by genes that regulate arch 1 and 2 development
  • related to hindbrain segmentation (rhombomere 4)
• Mouse
  • Hox a1/Hoxb1, goosecoid, Endothelin1, dHAND

Middle- tympanic cavity

• derived from first pharyngeal pouch
• extends as tubotympanic recess
• during week 5 recess contacts outer ear canal

mesoderm between 2 canals forms tympanic membrane

expands to form tympanic recess

stalk of recess forms eustacian tube

pharyngotympanic tube

Middle- Ossicles

• develop from first and second pharyngeal arches
• tympanic cavity enlarges to incorporate
• coats with epithelia

first arch mesoderm

• tensor tympani muscle
• malleus and incus

second arch mesoderm

• stapedius muscle and stapes

Middle Ear Genes

• gooscoid, RARs, Prx1, Otx2, Hoxa1, Hoxb1, endothelian related molecules

Inner- otocyst

• week 3 otic placode forms on surface ectoderm
• otic placode sinks into mesoderm
• forms otocyst (otic vesicle)
• Otic Vesicle to Labyrinth 1
• Pig stage 13/14 Otocyst
• Otocyst
• branches form and generate endolymphatic duct and sac
• forms vestibular and cochlear sac

Vestibular sac

• generates 3 expansions
• form semicircular ducts
• remainder forms utricle
• epithelia lining generates
• hair cells
• ampullary cristae
• utricular macula

Otic Vesicle to Labyrinth

• Human Stage 22
• Vestibular- Otoconia
• Otoconin- inner ear biominerals

Cochlear sac

• generates coiled cochlear duct
• humans 2 1/2 turns
• remainder forms saccule
• epithelia lining generates
• hair cells
• structures of organ of corti
• saccular macula
• Human Stage 22- cochlear
• Human Stage 22- cochlear

Bony Labyrinth

• formed from chrondified mesoderm
• Periotic Capsule
• mesenchyme within capsule degenerates to form space filled with perilymph

Vestibulocochlear Nerve

• forms beside otocyst
• from wall of otocyst and neural crest cells
• bipolar neurons
• vestibular neurons
  • outer end of internal acoustic meatus
  • innervate hair cells in membranous labyrinth
  • axons project to brain stem and synapse in vestibular nucleus
• cochlear neurons
  • cell bodies lie in modiolus
  • central pillar of cochlear
  • innervate hair cells of spiral organ
  • axons project to cochlear nucleus

Inner Ear Genes

• hindbrain segmentation occurs at same time placode arises
• otocyst adjacent to rhombomere 5
• may influence development
• Hoxa1, kreisler, Fgf3
• genes regulating neural crest cells (neural genes)
• Pax2 Ko affects cochlear and spiral ganglion, but not vestibular apparatus
• nerogenin 1 affects both ganglia

Semicircular canal

• Otx1- cochlear and vestibular normal

Hmx3, Prx1, Prx2

Sensory Organs

• thyroid hormone receptor beta
• Zebrafish-mindbomb mutant
  • excess hair cells but not supporting cells
    • Notch-Delta signaling

Gene Expression-inner ear

• Brn-3c and Hair cell development
• Supporting Cells- p27kip
• Thyroid Hormone
• Ganglion neurons require growth factors
• vestibular neurons- BDNF, NT3
  • survival not development

Congenital Deafness

• conductive- disease of outer and middle ear
• sensorineural- cochlear or central auditory pathway

Outer ear Malformation

• rare meatal atresia
• canal narrow or not formed
• part of first arch syndrome

Middle ear Malformation

• also rare
• can be part of first arch syndrome
• malformed maleus or incus
• congenital fixation of stapes
• stapes anchored to oval window
• annular ligament fails to develop

Congenital malformations Statistics

Congenital sensorineural

• hereditary or acquired
• see recent reviews

Hereditary

• recessive- severe
• dominant- mild
• can be associated with abnormal pigmentation
• hair and irises

Acquired

• rubella (German measles)
• maternal infection during 2nd month of pregnancy
• vaccination of young girls
• streptomycin
• antibiotic
• thalidomide

Conductive Hearing Loss

• produced by otitis media with effusion, is widespread in young children.
• temporary blockage of outer or middle ear
• See also: recent Ref and Senses WWW Link

Human Genes

LocusID Symbol Description Position Links 1678 DFN1 deafness, X-linked 1, progressive Xq22 1679 DFN2 deafness, X-linked 2, perceptive, congenital Xq22 1680 DFN4 deafness, X-linked 4, congenital sensorineural Xp21.2 1701 DFNB9 deafness, autosomal recessive 9 2p23-p22 1729 DIAPH1 diaphanous (Drosophila, homolog) 1 5q31 2706 GJB2 gap junction protein, beta 2, 26kD (connexin 26) 13q11-q12 4647 MYO7A myosin VIIA (Usher syndrome 1B (autosomal recessive, severe)) 11q13.5 5459 POU4F3 POU domain, class 4, transcription factor 3 5q31

Conductive Hearing Loss

• Conductive Hearing Loss Produces a Reversible Binaural Hearing Impairment David R. Moore, Jemma E. Hine, Ze Dong Jiang, Hiroaki Matsuda, Carl H. Parsons, and Andrew J. King J. Neurosci. 1999;19 8704-8711
  • http://www.jneurosci.org/cgi/content/abstract/19/19/8704
  • tested ferrets by lon-term plugging of ear canal
  • Repeated testing during the 22 months after unplugging revealed a gradual return to normal levels of unmasking.
  • Results show that a unilateral conductive hearing loss, in either infancy or adulthood, impairs binaural hearing both during and after the hearing loss.
  • Show scant evidence for adaptation to the plug and demonstrate a recovery from the impairment that occurs over a period of several months after restoration of normal peripheral function.

References

Molecular Normal Development

•  Jones JM, Montcouquiol M, Dabdoub A, Woods C, Kelley MW. [See Related Articles]  Inhibitors of differentiation and DNA binding (Ids) regulate Math1 and hair cell formation during the development of the organ of Corti. J Neurosci. 2006 Jan 11;26(2):550-8.
•  Kawamoto K, Ishimoto S, Minoda R, Brough DE, Raphael Y. [See Related Articles]  Math1 gene transfer generates new cochlear hair cells in mature guinea pigs in vivo. J Neurosci. 2003 Jun 1;23(11):4395-400.
•  Zine A, de Ribaupierre F. [See Related Articles]  Notch/Notch ligands and Math1 expression patterns in the organ of Corti of wild-type and Hes1 and Hes5 mutant mice. Hear Res. 2002 Aug;170(1-2):22-31.

List of recent Ear Development Reviews

Recent Reviews Abnormal Development

•  Webster WS. [See Related Articles]  Teratogen update: congenital rubella. Teratology. 1998 Jul;58(1):13-23. Review. PMID: 9699240; UI: 98364396.
• Yates JA, et al. [See Related Articles] Isolated congenital internal auditory canal atresia with normal facial nerve function. Int J Pediatr Otorhinolaryngol. 1997 Jul 18;41(1):1-8. Review.PMID: 9279630; UI: 97425580.
• Lambert PR, et al. [See Related Articles] Congenital malformations of the external auditory canal. Otolaryngol Clin North Am. 1996 Oct;29(5):741-60. Review. PMID: 8893214; UI: 97048378.
• Lin AE, et al.  [See Related Articles] Further delineation of the branchio-oculo-facial syndrome. Am J Med Genet. 1995 Mar 13;56(1):42-59. Review. MID: 7747785; UI: 95266633.
• Strasnick B, et al  [See Related Articles] Teratogenic hearing loss. J Am Acad Audiol. 1995 Jan;6(1):28-38. Review. PMID: 7696676; UI: 95210704.
• Kossowska E, et al. [See Related Articles] Prenatal and neonatal prophylaxis in otorhinolaryngology. Int J Pediatr Otorhinolaryngol. 1980 Jun;2(2):85-98. Review. PMID: 6765128; UI: 84160924.
• Gottlieb G. [See Related Articles] Conceptions of prenatal development: behavioral embryology. Psychol Rev. 1976 May;83(3):215-34. Review. No abstract available.
  PMID: 188059; UI: 77079452.
• Holme RH, Steel KP Genes involved in deafness. Curr Opin Genet Dev 1999 Jun;9(3):309-314
  • Remarkable progress has been made over the past few years in the field of hereditary deafness. To date, mutations in at least 35 genes are known to cause hearing loss. We are now beginning to understand the function of many of these genes, which affect diverse aspects of ear development and function.

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