Wnt/PKC Signaling Inhibits Sensory Hair Cell Formation in the Developing Mammalian Cochlea
Mulvaney, Joanna F; Layman, Erynn M; Feroze-Merzoug, Farhana; Abitbol, Julia M; Jones, Jennifer M; O'Connor, Dara; Naillat, Florence; Vainio, Seppo; Rubin, Jeffrey S; Kelley, Matthew W; Dabdoub, Alain (2025-06-12)
MDPI
12.06.2025
Mulvaney, J. F., Layman, E. M., Feroze-Merzoug, F., Abitbol, J. M., Jones, J. M., O’Connor, D., Naillat, F., Vainio, S., Rubin, J. S., Kelley, M. W., & Dabdoub, A. (2025). Wnt/PKC Signaling Inhibits Sensory Hair Cell Formation in the Developing Mammalian Cochlea. Cells, 14(12), 888. https://doi.org/10.3390/cells14120888
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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
https://creativecommons.org/licenses/by/4.0/
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
https://creativecommons.org/licenses/by/4.0/
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202506264978
https://urn.fi/URN:NBN:fi:oulu-202506264978
Tiivistelmä
Abstract
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.
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.
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