Wild-type cells rescue genotypically Math1-null hair cells in the inner ears of chimeric mice
Wild-type cells rescue genotypically Math1-null hair cells in the inner ears of chimeric mice
复制标题
DOI：
10.1016/j.ydbio.2007.02.028
复制
发表时间：
2007-05-15
影响因子：
2.7
通讯作者：
Hamre, Kristin M.
中科院分区：
文献类型：
--
作者：
Du, Xiaoping;Jensen, Patricia;Hamre, Kristin M.
转录因子Math 1已被证明在内耳毛细胞（HC）的形成中至关重要。然而，环境因素在HC特化中的影响表明，细胞外在因素对其发育也至关重要。为了测试外部因素是否影响Math 1-null（Math 1（beta-Gal/beta-Gal））HC的发育，我们检查了新生儿（出生后年龄P0-P4.5）Math 1-null嵌合小鼠，其中基因型突变体和野生型细胞混合形成内耳。我们提供了第一个直接的证据表明，Math 1-null HC能够在有利的嵌合环境中产生和生存。β-半乳糖苷酶表达用于鉴定遗传突变细胞，而细胞通过形态学特征，特别是HC特异性标志物的表达在表型上被定义为HC。在所有年龄段的内耳感觉上皮中均发现了基因型突变的HC。无论嵌合小鼠的野生型组分如何，都获得了相当的结果。因此，基因型突变的细胞保留分化成HC的能力。这意味着HC前体中Math 1基因的缺乏可以通过环境影响来克服，例如与野生型细胞的细胞间相互作用，最终导致HC的形成。爱思唯尔公司出版
The transcription factor Math1 has been shown to be critical in the formation of hair cells (HCs) in the inner ear. However, the influence of environmental factors in HC specification suggests that cell extrinsic factors are also crucial to their development. To test whether extrinsic factors impact development of Math1-null (Math1(beta-Gal/beta-Gal)) HCs, we examined neonatal (postnatal ages P0-P4.5) Math1-null chimeric mice in which genotypically mutant and wild-type cells intermingle to form the inner ear. We provide the first direct evidence that Math1-null HCs are able to be generated and survive in the conducive chimeric environment. beta-Galactosidase expression was used to identify genetically mutant cells while cells were phenotypically defined as HCs by morphological characteristics notably the expression of HC-specific markers. Genotypically mutant HCs were found in all sensory epithelia of the inner ear at all ages examined. Comparable results were obtained irrespective of the wild-type component of the chimeric mice. Thus, genotypically mutant cells retain the competence to differentiate into HCs. The implication is that the lack of the Math1 gene in HC precursors can be overcome by environmental influences, such as cell-cell interactions with wild-type cells, to ultimately result in the formation of HCs. Published by Elsevier Inc.