Table 1.

Genes affecting cochlear patterning

Gene	Type of protein	Distribution in the inner ear and surrounding structures	Mutant or knockout phenotype	Ref.
Brn4	Pou domain transcription factor	Periotic mesenchyme	Defects in fibroblasts of spiral ligament; shortened cochlea	48–51
Dlx 5	Homeobox transcription factor	Dorsal region of otic vesicle; semicircular canals and endolymphatic duct	No anterior or posterior canal; reduced lateral canal; abnormal endolymphatic duct and cochlea	25, 26
Eya 1	Transcriptional coactivator	Ventralmedial otic vesicle; VIIIth ganglion; vestibular and cochlear sensory regions; periotic mesenchyme	No VIIIth ganglion; amorphic inner ear	18, 22, 52, 53
Fgf3	Growth factor	r5 and r6; prospective otic placode region; neurogenic and sensory regions	No endolymphatic duct or sac; reduced spiral ganglion; enlarged membranous labyrinth	47, 54–57
Fgfr2 (IIIb)	Growth factor receptor	Otic placode; dorsal and medial wall of otic vesicle; nonsensory regions of the inner ear	Dysgenesis of membranous labyrinth; rudimentary sensory patches and VIIIth ganglion; 50% of mutants lack endolymphatic duct	47
Hoxa1	Homeobox transcription factor	8 dpc: r3/4 boundary to spinal cord	No endolymphatic duct or sac; amorphic inner ear; no organ of Corti; reduced VIIIth ganglion	58–61
Hoxa1/b1	Homeobox transcription factors	Hoxb1: 8 dpc: r3/4 boundary to spinal cord; 9 dpc: expression up-regulated in r4	Amorphic inner ear; more severe phenotype than Hoxa1−/− alone	62
Hoxa2	Homeobox transcription factor	r1/2 boundary to spinal cord; expression upregulated in r3 and r5	Membranous labyrinth appeared enlarged; scala vestibuli lacking or collapsed	63, 64
Kreisler	bZIP Transcription factor	r5 and r6	Misplaced otocyst; inner ear usually cyst-like; endolymphatic duct is often missing	56, 65–67
ngn 1	bHLH transcription factor	Anteroventrolateral otic vesicle	No VIIIth ganglion; fusion of utricle and saccule; shortened cochlea	11, 40
Otx1	Transcription factor	Lateral wall of otic vesicle; lateral canal and ampulla; lateral wall of saccule and cochlea	No lateral canal or ampulla; no lateral crista; incomplete separation of utricle and saccule; misshapen saccule and cochlea	10, 29
Otx2	Transcription factor	Ventral tip of otic vesicle; lateral wall of saccule and cochlea	Otx1−/−, Otx2+/−: more severe saccular and cochlear phenotype than Otx1−/−	10
Pax2	Paired-box transcription factor	Medial wall of otic vesicle; endolymphatic duct and sac; cochlea	Agenesis of the cochlea and spiral ganglion	17, 19, 68
Pax3	Paired-box transcription factor	Dorsal half of neural tube	Splotch mouse: aberrant endolymphatic duct; misshapen cochlear and vestibular components	69–73