Wnt/PKC Signaling Inhibits Sensory Hair Cell Formation in the Developing Mammalian Cochlea
The establishment of cell fate and boundaries between cell types is an essential step in development and organogenesis. In the mammalian cochlea, a distinct boundary exists between a medial region of non-sensory cells and a lateral region of sensory cells. We report that Wnt4 and sFRP2 act in combin...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/14/12/888 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849433192363196416 |
|---|---|
| author | Joanna F. Mulvaney Erynn M. Layman Farhana Feroze-Merzoug Julia M. Abitbol Jennifer M. Jones Dara O’Connor Florence Naillat Seppo Vainio Jeffrey S. Rubin Matthew W. Kelley Alain Dabdoub |
| author_facet | Joanna F. Mulvaney Erynn M. Layman Farhana Feroze-Merzoug Julia M. Abitbol Jennifer M. Jones Dara O’Connor Florence Naillat Seppo Vainio Jeffrey S. Rubin Matthew W. Kelley Alain Dabdoub |
| author_sort | Joanna F. Mulvaney |
| collection | DOAJ |
| description | The establishment of cell fate and boundaries between cell types is an essential step in development and organogenesis. In the mammalian cochlea, a distinct boundary exists between a medial region of non-sensory cells and a lateral region of sensory cells. We report that Wnt4 and sFRP2 act in combination to modulate the sensory cell differentiation of the organ of Corti. The hair cell inhibitory effects of Wnt4 in the inner ear are mediated through the activation of the non-canonical Wnt/Calcium/PKC pathway. We show that Wnt4 stimulates the activation of PKC in the cochlea, and that the inhibition of PKC rescues the ectopic Wnt4 activity phenotype. Finally, we demonstrate that modification at a PKC target site on Atoh1 diminishes its ability to induce hair cell formation. Ultimately, we identify a new Wnt/Calcium/PKC non-canonical signaling pathway that is involved in proper hair cell and organ of Corti formation in the developing mammalian cochlea. |
| format | Article |
| id | doaj-art-bacea1f2ffcf41f2af563e62c4e1fd07 |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-bacea1f2ffcf41f2af563e62c4e1fd072025-08-20T03:27:09ZengMDPI AGCells2073-44092025-06-01141288810.3390/cells14120888Wnt/PKC Signaling Inhibits Sensory Hair Cell Formation in the Developing Mammalian CochleaJoanna F. Mulvaney0Erynn M. Layman1Farhana Feroze-Merzoug2Julia M. Abitbol3Jennifer M. Jones4Dara O’Connor5Florence Naillat6Seppo Vainio7Jeffrey S. Rubin8Matthew W. Kelley9Alain Dabdoub10Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON M4N 3M5, CanadaLaboratory of Cochlear Development, NIDCD, National Institutes of Health, Bethesda, MD 20892, USALaboratory of Cellular and Molecular Biology, NCI, National Institutes of Health, Bethesda, MD 20892, USASunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON M4N 3M5, CanadaDepartment of Biology, Saint Mary’s College, Notre Dame, IN 46556, USASunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON M4N 3M5, CanadaDepartment of Biochemistry and Molecular Medicine, Biocenter and Infotech Oulu, University of Oulu, FIN-90014 Oulu, FinlandDepartment of Biochemistry and Molecular Medicine, Biocenter and Infotech Oulu, University of Oulu, FIN-90014 Oulu, FinlandLaboratory of Cellular and Molecular Biology, NCI, National Institutes of Health, Bethesda, MD 20892, USALaboratory of Cochlear Development, NIDCD, National Institutes of Health, Bethesda, MD 20892, USASunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON M4N 3M5, CanadaThe establishment of cell fate and boundaries between cell types is an essential step in development and organogenesis. In the mammalian cochlea, a distinct boundary exists between a medial region of non-sensory cells and a lateral region of sensory cells. We report that Wnt4 and sFRP2 act in combination to modulate the sensory cell differentiation of the organ of Corti. The hair cell inhibitory effects of Wnt4 in the inner ear are mediated through the activation of the non-canonical Wnt/Calcium/PKC pathway. We show that Wnt4 stimulates the activation of PKC in the cochlea, and that the inhibition of PKC rescues the ectopic Wnt4 activity phenotype. Finally, we demonstrate that modification at a PKC target site on Atoh1 diminishes its ability to induce hair cell formation. Ultimately, we identify a new Wnt/Calcium/PKC non-canonical signaling pathway that is involved in proper hair cell and organ of Corti formation in the developing mammalian cochlea.https://www.mdpi.com/2073-4409/14/12/888mousehearingcochleageneshair cell |
| spellingShingle | Joanna F. Mulvaney Erynn M. Layman Farhana Feroze-Merzoug Julia M. Abitbol Jennifer M. Jones Dara O’Connor Florence Naillat Seppo Vainio Jeffrey S. Rubin Matthew W. Kelley Alain Dabdoub Wnt/PKC Signaling Inhibits Sensory Hair Cell Formation in the Developing Mammalian Cochlea Cells mouse hearing cochlea genes hair cell |
| title | Wnt/PKC Signaling Inhibits Sensory Hair Cell Formation in the Developing Mammalian Cochlea |
| title_full | Wnt/PKC Signaling Inhibits Sensory Hair Cell Formation in the Developing Mammalian Cochlea |
| title_fullStr | Wnt/PKC Signaling Inhibits Sensory Hair Cell Formation in the Developing Mammalian Cochlea |
| title_full_unstemmed | Wnt/PKC Signaling Inhibits Sensory Hair Cell Formation in the Developing Mammalian Cochlea |
| title_short | Wnt/PKC Signaling Inhibits Sensory Hair Cell Formation in the Developing Mammalian Cochlea |
| title_sort | wnt pkc signaling inhibits sensory hair cell formation in the developing mammalian cochlea |
| topic | mouse hearing cochlea genes hair cell |
| url | https://www.mdpi.com/2073-4409/14/12/888 |
| work_keys_str_mv | AT joannafmulvaney wntpkcsignalinginhibitssensoryhaircellformationinthedevelopingmammaliancochlea AT erynnmlayman wntpkcsignalinginhibitssensoryhaircellformationinthedevelopingmammaliancochlea AT farhanaferozemerzoug wntpkcsignalinginhibitssensoryhaircellformationinthedevelopingmammaliancochlea AT juliamabitbol wntpkcsignalinginhibitssensoryhaircellformationinthedevelopingmammaliancochlea AT jennifermjones wntpkcsignalinginhibitssensoryhaircellformationinthedevelopingmammaliancochlea AT daraoconnor wntpkcsignalinginhibitssensoryhaircellformationinthedevelopingmammaliancochlea AT florencenaillat wntpkcsignalinginhibitssensoryhaircellformationinthedevelopingmammaliancochlea AT seppovainio wntpkcsignalinginhibitssensoryhaircellformationinthedevelopingmammaliancochlea AT jeffreysrubin wntpkcsignalinginhibitssensoryhaircellformationinthedevelopingmammaliancochlea AT matthewwkelley wntpkcsignalinginhibitssensoryhaircellformationinthedevelopingmammaliancochlea AT alaindabdoub wntpkcsignalinginhibitssensoryhaircellformationinthedevelopingmammaliancochlea |