Loss of Pax3 causes reduction of melanocytes in the developing mouse cochlea.
Loss of Pax3 causes reduction of melanocytes in the developing mouse cochlea.
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DOI：
10.1038/s41598-024-52629-9
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发表时间：
2024-01-26
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
耳蜗黑素细胞是血管纹中的中间细胞，产生听觉功能所需的耳蜗内电位。人类PAX 3突变导致Waardenburg综合征以及皮肤和视网膜黑色素细胞异常，表现为先天性听力损失（约70%）以及皮肤、毛发和眼睛色素减退。然而，听力损失的潜在机制仍不清楚。血管纹中的黑素细胞来源于Pax 3追踪的成黑素细胞和Plp 1追踪的雪旺氏细胞前体，两者都来源于神经嵴细胞。在这里，使用Pax 3-Cre基因敲入小鼠，允许Pax 3表达细胞的谱系追踪和Pax 3的破坏，我们发现Pax 3缺陷导致耳蜗缩短，前庭器官畸形和神经管缺陷。谱系追踪和原位杂交显示Pax 3+衍生物有助于发育中的血管纹中的S100+、Kir4.1+和Dct+黑素细胞（中间细胞），所有这些在Pax 3突变动物中均显著减少。综上所述，这些结果表明，Pax 3是神经嵴细胞衍生的耳蜗黑素细胞的发育所必需的，其缺失可能导致人类先天性听力损失Waardenburg综合征。
Cochlear melanocytes are intermediate cells in the stria vascularis that generate endocochlear potentials required for auditory function. Human PAX3 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 Pax3-traced melanoblasts and Plp1-traced Schwann cell precursors, both of which derive from neural crest cells. Here, using a Pax3-Cre knock-in mouse that allows lineage tracing of Pax3-expressing cells and disruption of Pax3, we found that Pax3 deficiency causes foreshortened cochlea, malformed vestibular apparatus, and neural tube defects. Lineage tracing and in situ hybridization show that Pax3+ derivatives contribute to S100+, Kir4.1+ and Dct+ melanocytes (intermediate cells) in the developing stria vascularis, all of which are significantly diminished in Pax3 mutant animals. Taken together, these results suggest that Pax3 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.
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影响因子：
5.5
作者：
Marcus, DC;Wu, T;Kofuji, P
通讯作者：
Kofuji, P
影响因子：
4.3
作者：
Renauld JM;Davis W;Cai T;Cabrera C;Basch ML
通讯作者：
Basch ML
DOI：
10.1073/pnas.90.2.532
发表时间：
1993-01-15
影响因子：
11.1
作者：
EPSTEIN, DJ;VOGAN, KJ;GROS, P
通讯作者：
GROS, P
影响因子：
3.5
作者：
Bondurand, N;Pingault, V;Goossens, M
通讯作者：
Goossens, M
DOI：
10.1073/pnas.1219124110
发表时间：
2013-04-02
影响因子：
11.1
作者：
Milet, Cecile;Maczkowiak, Frederique;Monsoro-Burq, Anne Helene
通讯作者：
Monsoro-Burq, Anne Helene