Spatiotemporal pattern and isoforms of cadherin 23 in wild type and waltzer mice during inner ear hair cell development
Spatiotemporal pattern and isoforms of cadherin 23 in wild type and waltzer mice during inner ear hair cell development
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DOI：
10.1016/j.ydbio.2005.01.015
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发表时间：
2005-04-15
影响因子：
2.7
通讯作者：
Friedman, TB
中科院分区：
文献类型：
--
作者：
Lagziel, A;Ahmed, ZM;Friedman, TB
编码钙粘蛋白 23 的基因的突变等位基因与 1 型亚瑟综合征 (USH1D)、人类孤立性耳聋 (DFNB12) 以及华尔兹 (v) 小鼠的耳聋和转圈行为有关。华尔兹小鼠的立体纤毛紊乱且动纤毛错位，表明钙粘蛋白 23 对于发束发育的重要性。钙粘蛋白 23 定位于静纤毛的发育，并被提议作为尖端连接的组成部分。我们发现，在内耳发育过程中，钙粘蛋白 23 最初在 E14.5 的中心体中检测到，然后沿着新兴静纤毛的长度检测，后来集中在静纤毛的顶部，随后从顶部消失。在成熟的前庭毛束中，钙粘蛋白 23 沿着动纤毛和粪纤毛-动纤毛键区域存在，这是哺乳动物、小鸡和青蛙中保守的模式。在整个开发过程中，钙粘蛋白 23 也存在于 Reissner 膜 (RM) 中。在纯合 v(6J) 小鼠中，据报道，静纤毛中不存在已报道的无效等位基因钙粘蛋白 23，但存在于动纤毛、RM 和中心体中。我们通过鉴定序列和表达不受 v(6J) 等位基因影响的两种新的 Cdh23 亚型来协调这些结果。我们的结果表明，Cdh23 参与静纤毛链接可能仅限于发育发束。由爱思唯尔公司出版
Mutant alleles of the gene encoding cadherin 23 are associated with Usher syndrome type 1 (USH1D), isolated deafness (DFNB12) in humans, and deafness and circling behavior in waltzer (v) mice. Stereocilia of waltzer mice are disorganized and the kinocilia misplaced, indicating the importance of cadherin 23 for hair bundle development. Cadherin 23 was localized to developing stereocilia and proposed as a component of the tip link. We show that, during development of the inner ear, cadherin 23 is initially detected in centrosomes at E14.5, then along the length of emerging stereocilia, and later becomes concentrated at and subsequently disappears from the tops of stereocilia. In mature vestibular hair bundles, cadherin 23 is present along the kinocilium and in the region of stercocilia-kinocilium bonds, a pattern conserved in mammals, chicks, and frogs. Cadherin 23 is also present in Reissner's membrane (RM) throughout development. In homozygous v(6J) mice, a reported null allele, cadherin 23 was absent from stereocilia, but present in kinocilia, RM, and centrosomes. We reconciled these results by identifying two novel isoforms of Cdh23 unaffected in sequence and expression by the v(6J) allele. Our results suggest that Cdh23 participation in stereocilia links may be restricted to developing hair bundles. Published by Elsevier Inc.