Table 1.
Summary of the available spatiotemporal expression data for deafness-related genes (column 1) in inner ear organoids (column 2) and the rodent inner ear (column 3)
| Gene | Expression pattern in inner ear organoids | In vivo expression pattern | Disorder | Clinical findings |
|---|---|---|---|---|
| ACTG1 | Expressed in mouse otic-like epithelium and hair bundle-like structures by day 20 (Koehler et al. 2013; Liu et al 2016; Perny et al. 2017; Schaefer et al. 2018; Tang et al. 2019); expressed in human otic-like epithelium and hair bundle-like structures by day 60 (Koehler et al. 2017) | Expressed in the stereocilia, cuticular plates, and adherens junctions of mouse HCs by E16.5 (Andrade 2015) | DFNA20/26 | Progressive postlingual high-frequency SNHL (van Wijk et al. 2003; Zhu et al. 2003) |
| CDH23 | Expressed in mouse hair bundle-like structures by day 23 (Tang et al. 2019) | Expressed in mouse cochlear and vestibular HCs as early as E16.5a and E14.5, respectively, persists to at least P16; expressed in Reissner’s membrane from E16.5 onward (Lagziel et al. 2005) | Usher syndrome type 1D | Profound congenital SNHL, vestibular dysfunction, retinitis pigmentosa (Bolz et al. 2001; Bork et al. 2001) |
| DFNB12 | Profound congenital SNHL (Bork et al. 2001) | |||
| ESPN | Expressed in mouse hair bundle-like structures by day 20 (DeJonge et al. 2016; Hartman et al. 2018; Koehler et al. 2013; Liu et al. 2016; Tang et al. 2019); expressed in human hair bundle-like structures by day 70 (Koehler et al. 2017) | Expressed in the rat otic pit, vesicle, and epithelium by E10, enriched in vestibular, inner, and outer HCs as early as E14, E16, and E18, respectivelya (Sekerkova et al. 2006) | DFNB36 | Profound prelingual SNHL, vestibular dysfunction (Naz et al. 2004) |
| EYA1 | Expressed in mouse otic-like vesicles at day 12 (Schaefer et al. 2018) | Expressed in the ventral aspect of the mouse otic vesicle at E9.5–E11.5; expressed in the otic sensory epithelium from E12.5 to birth, restricted to vestibular HCs and cochlear sensory epithelium by P20; expressed in the vestibulocochlear ganglion by E10.5, persists to at least P20; expressed in the vestibular transitional epithelium from E15.5 to E17.5, the saccular roof from E15.5 to birth, and the spiral ligament at P8 (Kalatzis et al. 1998; Xu et al. 2021; Zheng et al. 2003) | Branchio-oto-renal spectrum disorders | Sensorineural, conductive, or mixed HL, branchial arch anomalies, renal/urinary tract abnormalities (Abdelhak et al. 1997; Vincent et al. 1997) |
| MYO6 | Expressed in mouse HC-like cells by day 17 (Hartman et al. 2018) | Expressed in mouse HCs as early as E13.5 (Xiang et al. 1998) | DFNA22 | Progressive postlingual high-frequency SNHL (Melchionda et al. 2001) |
| DFNB37 | Severe-to-profound congenital SNHL, vestibular dysfunction (Ahmed et al. 2003a) | |||
| MYO7A | Expressed in mouse otic-like vesicles at day 14, restricted to HC-like cells by day 15 (DeJonge et al. 2016; Hartman et al. 2018; Koehler et al. 2013; Liu et al. 2016; Perny et al. 2017; Schaefer et al. 2018; Tang et al. 2019); expressed in human HC-like cells by day 60 (Koehler et al. 2017) | Expressed in mouse HCs as early as E13.5 (Xiang et al. 1998) | Usher syndrome type 1B | Profound congenital SNHL, vestibular dysfunction, retinitis pigmentosa (Weil et al. 1995) |
| DFNA11 | Progressive postlingual SNHL (Liu et al. 1997b) | |||
| DFNB2 | Profound SNHL, vestibular dysfunction (Liu et al. 1997a; Weil et al. 1997) | |||
| PCDH15 | Expressed in mouse hair bundle-like structures by day 23 (Tang et al. 2019) | Expressed in the mouse cochlear HCs by P3a; expressed in vestibular HCs as early as E15.5 (Ahmed et al. 2006)b | Usher syndrome type 1F | Profound congenital SNHL, vestibular dysfunction, retinitis pigmentosa (Ahmed et al. 2001; Alagramam et al. 2001) |
| DFNB23 | Severe-to-profound prelingual SNHL (Ahmed et al. 2003b) | |||
| POU4F3 | Expressed in mouse HC-like cells by day 16 (DeJonge et al. 2016; Koehler et al. 2013; Tang et al. 2019); expressed in human HC-like cells by day 140 (Koehler et al. 2017) | Expressed in mouse HCs as early as E12.5 (Xiang et al. 1998) | DFNA15 | Progressive postlingual high-frequency SNHL, vestibular dysfunction (Vahava et al. 1998) |
| SIX1 | Expressed in the outer epithelium of mPSC-derived aggregates at d6, restricted to otic-like vesicles at day 12 (Koehler et al. 2013; Schaefer et al. 2018) | Expressed in the ventral aspect of the mouse otic pit and vesicle from E8.75 to E10.5, expressed in the vestibular sensory epithelium and greater and lesser epithelial ridges at E12.5, restricted to the vestibular and cochlear HCs,a greater epithelial ridge, and stria vascularis as early as E15.5; expressed in the vestibulocochlear ganglion at E12.5 (Xu et al. 2021; Zheng et al. 2003) | Branchio-oto-renal spectrum disorders | Sensorineural, conductive, or mixed HL, branchial arch anomalies, renal/urinary tract abnormalities (Ruf et al. 2004) |
| DFNA23 | Sensorineural or mixed HL (Mosrati et al. 2011) | |||
| SOX10 | Expressed in human otic-like pits and vesicles at days 14–35, restricted to SC-like cells and non-sensory otic-like epithelium by day 75; expressed in cranial neural crest-like cells at day 35 (Koehler et al. 2017) | Expressed in the mouse otic pit, vesicle, and epithelium from E9.0 to E16.5, restricted to the SCs and non-sensory otic epithelium by P1, persists to at least P21, except in tympanic border cells; expressed in migrating cranial neural crest cells from E10.5 to E14.5, persists in cranial neural crest derivatives (intermediate and glial cells) to at least P21 (Wakaoka et al. 2013) | Waardenburg syndrome type 2E | Profound prelingual SNHL, pigmentation abnormalities (Bondurand et al. 2007) |
| Waardenburg syndrome type 4C | Profound congenital SNHL, pigmentation abnormalities, Hirschsprung disease (Pingault et al. 1998) |
The associated genetic disease(s) (column 4) and its/their clinical findings (column 5) are provided for the reader’s reference
HC hair cell, HL hearing loss, mPSC mouse pluripotent stem cell, P postnatal day, SC support cell, SNHL sensorineural hearing loss
aHC-specific gene expression commences in a basal-to-apical direction along the cochlear duct, with the embryonic date (E) provided here denoting onset at the cochlear base
bPCDH15 has several isoforms with distinct spatiotemporal expression patterns