Loss of Pax3 causes reduction of melanocytes in the developing mouse cochlea

Tomokatsu Udagawa, Erisa Takahashi, Norifumi Tatsumi, Hideki Mutai, Hiroki Saijo, Yuko Kondo, Patrick J. Atkinson, Tatsuo Matsunaga, Mamoru Yoshikawa, Hiromi Kojima, Masataka Okabe, Alan G. Cheng

doi:10.1038/s41598-024-52629-9

<jats:title>Abstract</jats:title><jats:p>Cochlear melanocytes are intermediate cells in the stria vascularis that generate endocochlear potentials required for auditory function. Human <jats:italic>PAX3</jats:italic> mutations cause Waardenburg syndrome and abnormalities of skin and retinal melanocytes, manifested as congenital hearing loss (~ 70%) and hypopigmentation of skin, hair and eyes. However, the underlying mechanism of hearing loss remains unclear. Cochlear melanocytes in the stria vascularis originated from <jats:italic>Pax3</jats:italic>-traced melanoblasts and <jats:italic>Plp1</jats:italic>-traced Schwann cell precursors, both of which derive from neural crest cells. Here, using a <jats:italic>Pax3-Cre</jats:italic> knock-in mouse that allows lineage tracing of <jats:italic>Pax3</jats:italic>-expressing cells and disruption of <jats:italic>Pax3</jats:italic>, we found that Pax3 deficiency causes foreshortened cochlea, malformed vestibular apparatus, and neural tube defects. Lineage tracing and in situ hybridization show that <jats:italic>Pax3</jats:italic><jats:sup>+</jats:sup> derivatives contribute to S100<jats:sup>+</jats:sup>, <jats:italic>Kir4.1</jats:italic><jats:sup>+</jats:sup> and <jats:italic>Dct</jats:italic><jats:sup>+</jats:sup> melanocytes (intermediate cells) in the developing stria vascularis, all of which are significantly diminished in <jats:italic>Pax3</jats:italic> mutant animals. Taken together, these results suggest that <jats:italic>Pax3</jats:italic> is required for the development of neural crest cell-derived cochlear melanocytes, whose absence may contribute to congenital hearing loss of Waardenburg syndrome in humans.</jats:p>

Loss of Pax3 causes reduction of melanocytes in the developing mouse cochlea

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