Inner Ear Development

• Review of adult anatomy and physiology

• Generation of specification of the sensory organs

• Birth and differentiation of hair cells

Tonotopic Maps

Organ of Corti

Hair Cells

Hair Cell Function

Stereocilia Damage (Sensorineural Hearing Loss) 

Rabinowitz (1991)

Inner Ear Development

• Review of adult anatomy and physiology

• Generation of specification of the sensory organ

• Birth and differentiation of hair cells

Primary Neurulation (formation of neural tube) 

MHP=medial hinge point 

Neural groove

Sensory Placodes (outside neural crest)

Formation of Sensory Ganglia 

Streit (2007) 

• Before the placodes have emerged, head ectoderm cells have become distinct re. final placement in a specific placode o This region is called the preplacodal region

Differentiation of Preplacodal

Region

• Inhibitory signals from the lateral (BMP) and posterior (Wnt) ectoderm, as well as mesoderm and the neural folds define preplacodal region 

Streit (2007)

Otic Placode à Otic Pit

• Otic placode is an ectodermal thickening adjacent to the rhombenscephalon

• Invaginates to form the otic pit

Otic Pit à Otic Vesicle

• Pinching off of otic pit • Forms just after neural tube closure • Forms hair cells and spiral ganglion cells as well

as accessory structures

Formation of the Pro-sensory Patch

• forms in the ventromedial wall • defined by expression patterns of Serrate1,

Lunatic fringe and BEN à involved in Notch signaling

• asymmetric expression patterns of these and other molecules appear to define ventral vs. dorsal halves, and anterior/posterior compartments

Appearance of Specific Sensory Organs

• defined by the appearance of BMP4 (member of TGF-β growth factor family)

• BMP4 appears to control development of accessory structures, not hair cells (e.g., Noggin disrupts semicircular canal formation but not generation of vestibular hair cells)

Inner Ear Development

• Review of adult anatomy and physiology

• Generation of specification of the sensory organs

• Birth and differentiation of hair cells o Cell fate o Stereocilia polarity o Outer vs. inner

Birth and generation of hair cells

• shortly after specification of the prosensory patches, “organ of Corti” cells stop dividing

• defined by the expression of p27 Kip1 , a cyclin-dependent kinase inhibitor

• at any one place along the cochlear duct, hair and supporting cells are born simultaneously

• a given progenitor cell can produce two supporting cells, two hair cells or both cell types

Kelley (2007)

Cell Fate (Early)

• 4 potential fates • Decision by prosensory

cells to become a hair cell or a supporting cell involves LATERAL INHIBITION mediated by Notch signalling 

Kelley (2007)

Cell Fate (Late)

• nascent hair cells begin to express Brn3.1, a POU domain transcription factor that is specifically expressed by hair cells

• a day later, the hair cell markers myosin VI and VIIa are expressed

Stereocilia Polarity

Stereocilia Polarity

• initially, small stereocilia sprout over the entire apical surface, clustered around a centrally located kinocilium

• kinocilium migrates to one side of the cell, and the stereocilia nearest the kinocilium elongate

• rootlets extend down from the stereocilia, anchoring them into the cuticular plate

• excess stereocilia and kinocilium are reabsorbed

• tip links between the stereocilia are formed 

Denman­Johnson and Forge (1999)

Regulation of Stereocilia Formation 

Nayak et al. (2007)

Inner vs. Outer Hair Cells

• expression of PRESTIN