Limits...
Auditory hair cell defects as potential cause for sensorineural deafness in Wolf-Hirschhorn syndrome.

Ahmed M, Ura K, Streit A - Dis Model Mech (2015)

Bottom Line: Although auditory hair cells are specified normally, their stereocilia hair bundles required for sound perception fail to develop the appropriate morphology.Furthermore, the orientation and cellular organisation of cochlear hair cells and their innervation are defective.These findings identify, for the first time, the likely cause of sensorineural hearing loss in individuals with WHS.

View Article: PubMed Central - PubMed

Affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London, London, SE1 9RT, UK.

No MeSH data available.


Related in: MedlinePlus

Organisation of spiral fibres is disrupted in WHSC1 mutant cochleae. Basal region of E18.5 wild-type and mutant organ of Corti immunostained for neurofilament (red), phalloidin (green) and Hoechst (blue). The innervations pattern appears normal as spiral ganglia fibres project towards their hair cell targets (A,E,I). However, whereas fibres crossing the tunnel of Corti (TC) turn basally and fasciculate to form three distinct rows in wild type (C,D), they fail to fasciculate in heterozygous and homozygous mutants (G,H,K,L). Note the orderly arrangement of similarly shaped and sized hair cells in wild-type (B) versus disorganised arrangement in mutant (F,J) cochleae. Scale bars: 30 μm (A,E,I); 10 μm (B-D,F-H,J-L). TC, tunnel of Corti; S1-S3, spiral fibre rows; O1-O4, outer hair cell rows; IHC, inner hair cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4582100&req=5

DMM019547F6: Organisation of spiral fibres is disrupted in WHSC1 mutant cochleae. Basal region of E18.5 wild-type and mutant organ of Corti immunostained for neurofilament (red), phalloidin (green) and Hoechst (blue). The innervations pattern appears normal as spiral ganglia fibres project towards their hair cell targets (A,E,I). However, whereas fibres crossing the tunnel of Corti (TC) turn basally and fasciculate to form three distinct rows in wild type (C,D), they fail to fasciculate in heterozygous and homozygous mutants (G,H,K,L). Note the orderly arrangement of similarly shaped and sized hair cells in wild-type (B) versus disorganised arrangement in mutant (F,J) cochleae. Scale bars: 30 μm (A,E,I); 10 μm (B-D,F-H,J-L). TC, tunnel of Corti; S1-S3, spiral fibre rows; O1-O4, outer hair cell rows; IHC, inner hair cells.

Mentions: As sensorineural hearing loss can also be caused by abnormalities in the bipolar spiral ganglia neurons that innervate hair cells, we performed immunolabelling for neurofilament (NF) to detect neuronal fibres. Spiral ganglion projections to IHCs appear to be normal but more fibres seem to target the OHCs (Figs 5G-J and 6). In WHSC1+/+ cochleae, the majority of fibres terminate on the IHCs, while some cross the tunnel of Corti, turn towards the base and form three rows of spiral fibres (Fig. 6A-D). This arrangement of fibres is disrupted in both WHSC1+/− (Fig. 6E-H; n=3/25) and WHSC1−/− (Fig. 6I-L; n=7/11) cochleae. Together these findings suggest that WHSC1 function is required for the organisation of spiral fibres, in addition to hair cell arrangement.Fig. 6.


Auditory hair cell defects as potential cause for sensorineural deafness in Wolf-Hirschhorn syndrome.

Ahmed M, Ura K, Streit A - Dis Model Mech (2015)

Organisation of spiral fibres is disrupted in WHSC1 mutant cochleae. Basal region of E18.5 wild-type and mutant organ of Corti immunostained for neurofilament (red), phalloidin (green) and Hoechst (blue). The innervations pattern appears normal as spiral ganglia fibres project towards their hair cell targets (A,E,I). However, whereas fibres crossing the tunnel of Corti (TC) turn basally and fasciculate to form three distinct rows in wild type (C,D), they fail to fasciculate in heterozygous and homozygous mutants (G,H,K,L). Note the orderly arrangement of similarly shaped and sized hair cells in wild-type (B) versus disorganised arrangement in mutant (F,J) cochleae. Scale bars: 30 μm (A,E,I); 10 μm (B-D,F-H,J-L). TC, tunnel of Corti; S1-S3, spiral fibre rows; O1-O4, outer hair cell rows; IHC, inner hair cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4582100&req=5

DMM019547F6: Organisation of spiral fibres is disrupted in WHSC1 mutant cochleae. Basal region of E18.5 wild-type and mutant organ of Corti immunostained for neurofilament (red), phalloidin (green) and Hoechst (blue). The innervations pattern appears normal as spiral ganglia fibres project towards their hair cell targets (A,E,I). However, whereas fibres crossing the tunnel of Corti (TC) turn basally and fasciculate to form three distinct rows in wild type (C,D), they fail to fasciculate in heterozygous and homozygous mutants (G,H,K,L). Note the orderly arrangement of similarly shaped and sized hair cells in wild-type (B) versus disorganised arrangement in mutant (F,J) cochleae. Scale bars: 30 μm (A,E,I); 10 μm (B-D,F-H,J-L). TC, tunnel of Corti; S1-S3, spiral fibre rows; O1-O4, outer hair cell rows; IHC, inner hair cells.
Mentions: As sensorineural hearing loss can also be caused by abnormalities in the bipolar spiral ganglia neurons that innervate hair cells, we performed immunolabelling for neurofilament (NF) to detect neuronal fibres. Spiral ganglion projections to IHCs appear to be normal but more fibres seem to target the OHCs (Figs 5G-J and 6). In WHSC1+/+ cochleae, the majority of fibres terminate on the IHCs, while some cross the tunnel of Corti, turn towards the base and form three rows of spiral fibres (Fig. 6A-D). This arrangement of fibres is disrupted in both WHSC1+/− (Fig. 6E-H; n=3/25) and WHSC1−/− (Fig. 6I-L; n=7/11) cochleae. Together these findings suggest that WHSC1 function is required for the organisation of spiral fibres, in addition to hair cell arrangement.Fig. 6.

Bottom Line: Although auditory hair cells are specified normally, their stereocilia hair bundles required for sound perception fail to develop the appropriate morphology.Furthermore, the orientation and cellular organisation of cochlear hair cells and their innervation are defective.These findings identify, for the first time, the likely cause of sensorineural hearing loss in individuals with WHS.

View Article: PubMed Central - PubMed

Affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London, London, SE1 9RT, UK.

No MeSH data available.


Related in: MedlinePlus