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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

Auditory hair cells are disorganised in WHSC1−/− mice. (A-F) E18.5 wild-type and mutant organ of Corti immunostained for MYO7A (green). Differences in cell shape and size affect the arrangement of hair cells. (G-J) MYO7A and neurofilament (red) staining in sections show more spiral ganglia neuron (SGN) fibres towards outer hair cells in WHSC1−/− mice; nuclei stained with Hoechst (blue). Scale bars: 10 μm (A-F,I,J); 30 μm (G,H). (I,J) Higher magnifications of the white boxed regions in G and H, respectively. Arrowheads, hair cells; asterisk, hair cell squeezed in between other hair cells. Mid, middle region of the cochlea.
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DMM019547F5: Auditory hair cells are disorganised in WHSC1−/− mice. (A-F) E18.5 wild-type and mutant organ of Corti immunostained for MYO7A (green). Differences in cell shape and size affect the arrangement of hair cells. (G-J) MYO7A and neurofilament (red) staining in sections show more spiral ganglia neuron (SGN) fibres towards outer hair cells in WHSC1−/− mice; nuclei stained with Hoechst (blue). Scale bars: 10 μm (A-F,I,J); 30 μm (G,H). (I,J) Higher magnifications of the white boxed regions in G and H, respectively. Arrowheads, hair cells; asterisk, hair cell squeezed in between other hair cells. Mid, middle region of the cochlea.

Mentions: To investigate the hair cell phenotype further, we analysed E18.5 cochlea immunostained for MYO7A by confocal microscopy. We found a striking difference in size and shape between mutant and wild-type cochlear hair cells. Whereas all hair cells appeared similar in size in WHSC1+/+ cochlea, their size varied from normal to small in WHSC1−/− mice (Fig. 4A,B), and to a lesser extent in WHSC1+/− mice (supplementary material Fig. S3G). These differences seem to affect the intercellular space: in mutant mice some hair cells made contact with many other cells (without any intercellular gaps), whereas other cells (especially IHCs) are more spaced out, not establishing any contacts at all (Fig. 5A-F). This hair cell disorganisation was also observed in sections (Fig. 5G-J, arrowheads), where extra cells seem to be squeezed between existing cells (in this case OHCs, Fig. 5H,J, asterisk). The inner pillar cells were present and seemed to be normal (supplementary material Fig. S3), although one inner pillar cell was missing in WHSC1+/− cochlea (supplementary material Fig. S3I,J, arrow; n=1/13).Fig. 5.


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

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

Auditory hair cells are disorganised in WHSC1−/− mice. (A-F) E18.5 wild-type and mutant organ of Corti immunostained for MYO7A (green). Differences in cell shape and size affect the arrangement of hair cells. (G-J) MYO7A and neurofilament (red) staining in sections show more spiral ganglia neuron (SGN) fibres towards outer hair cells in WHSC1−/− mice; nuclei stained with Hoechst (blue). Scale bars: 10 μm (A-F,I,J); 30 μm (G,H). (I,J) Higher magnifications of the white boxed regions in G and H, respectively. Arrowheads, hair cells; asterisk, hair cell squeezed in between other hair cells. Mid, middle region of the cochlea.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

DMM019547F5: Auditory hair cells are disorganised in WHSC1−/− mice. (A-F) E18.5 wild-type and mutant organ of Corti immunostained for MYO7A (green). Differences in cell shape and size affect the arrangement of hair cells. (G-J) MYO7A and neurofilament (red) staining in sections show more spiral ganglia neuron (SGN) fibres towards outer hair cells in WHSC1−/− mice; nuclei stained with Hoechst (blue). Scale bars: 10 μm (A-F,I,J); 30 μm (G,H). (I,J) Higher magnifications of the white boxed regions in G and H, respectively. Arrowheads, hair cells; asterisk, hair cell squeezed in between other hair cells. Mid, middle region of the cochlea.
Mentions: To investigate the hair cell phenotype further, we analysed E18.5 cochlea immunostained for MYO7A by confocal microscopy. We found a striking difference in size and shape between mutant and wild-type cochlear hair cells. Whereas all hair cells appeared similar in size in WHSC1+/+ cochlea, their size varied from normal to small in WHSC1−/− mice (Fig. 4A,B), and to a lesser extent in WHSC1+/− mice (supplementary material Fig. S3G). These differences seem to affect the intercellular space: in mutant mice some hair cells made contact with many other cells (without any intercellular gaps), whereas other cells (especially IHCs) are more spaced out, not establishing any contacts at all (Fig. 5A-F). This hair cell disorganisation was also observed in sections (Fig. 5G-J, arrowheads), where extra cells seem to be squeezed between existing cells (in this case OHCs, Fig. 5H,J, asterisk). The inner pillar cells were present and seemed to be normal (supplementary material Fig. S3), although one inner pillar cell was missing in WHSC1+/− cochlea (supplementary material Fig. S3I,J, arrow; n=1/13).Fig. 5.

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