Otx1 and Otx2 activities are required for the normal development of the mouse inner ear.
Otx1 and Otx2 activities are required for the normal development of the mouse inner ear.
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发表时间：
1999-06
期刊：
影响因子：
4.6
通讯作者：
H. Morsli;F. Tuorto;Daniel I. Choo;M. Postiglione;Antonio Simeone;Doris K. Wu
中科院分区：
文献类型：
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作者：
H. Morsli;F. Tuorto;Daniel I. Choo;M. Postiglione;Antonio Simeone;Doris K. Wu
Otx1 和 Otx2 基因是果蝇 Orthodenticle (Otd) 基因的两个鼠类直系同源物。在发育中的小鼠胚胎中，两种 Otx 基因均在头端区域和某些感觉器官（例如内耳）中表达。先前的研究表明，缺乏 Otx1 的小鼠表现出异常的大脑模式，而缺乏 Otx2 的胚胎发育时没有头部。在这项研究中，我们检查了不同发育阶段同时缺乏 Otx1 和 Otx2 基因的小鼠的内耳。在野生型内耳中，Otx1 在侧耳管和壶腹以及部分椭圆囊中表达，但 Otx2 不表达。在假定椭圆囊的中层腹侧，Otx1 和 Otx2 在球囊和耳蜗等区域共表达。 Otx1-/-突变体的充满油漆的膜迷路显示出外侧半规管、外侧壶腹、囊囊管和耳蜗囊管的缺失，以及耳蜗的不明确的钩（近端部分）。 Otx1-/- 小鼠的球囊和耳蜗形状缺陷各不相同，并且在 Otx1-/-;Otx2(+/-)- 背景中更为严重。 Otx1-/-和Otx1-/-;Otx2(+/)-突变体的组织学和原位杂交实验表明侧嵴缺失。此外，椭圆囊和球囊的黄斑部分融合。在突变小鼠中，两个 Otx1 基因拷贝均被人类 Otx2 cDNA (hOtx2(1)/hOtx2(1)) 取代，大多数与 Otx1-/- 突变体相关的缺陷都得到了挽救。然而，在内耳内，hOtx2 表达未能挽救侧耳管和壶腹表型，并且仅在 Otx1 和 Otx2 均正常表达的区域观察到不同的挽救。这些结果表明，两个 Otx 基因在小鼠内耳的形态发生及其感觉器官的发育中发挥着重要且不同的作用。
The Otx1 and Otx2 genes are two murine orthologues of the Orthodenticle (Otd) gene in Drosophila. In the developing mouse embryo, both Otx genes are expressed in the rostral head region and in certain sense organs such as the inner ear. Previous studies have shown that mice lacking Otx1 display abnormal patterning of the brain, whereas embryos lacking Otx2 develop without heads. In this study, we examined, at different developmental stages, the inner ears of mice lacking both Otx1 and Otx2 genes. In wild-type inner ears, Otx1, but not Otx2, was expressed in the lateral canal and ampulla, as well as part of the utricle. Ventral to the mid-level of the presumptive utricle, Otx1 and Otx2 were co-expressed, in regions such as the saccule and cochlea. Paint-filled membranous labyrinths of Otx1-/- mutants showed an absence of the lateral semicircular canal, lateral ampulla, utriculosaccular duct and cochleosaccular duct, and a poorly defined hook (the proximal part) of the cochlea. Defects in the shape of the saccule and cochlea were variable in Otx1-/- mice and were much more severe in an Otx1-/-;Otx2(+/)- background. Histological and in situ hybridization experiments of both Otx1-/- and Otx1-/-;Otx2(+/)- mutants revealed that the lateral crista was absent. In addition, the maculae of the utricle and saccule were partially fused. In mutant mice in which both copies of the Otx1 gene were replaced with a human Otx2 cDNA (hOtx2(1)/ hOtx2(1)), most of the defects associated with Otx1-/- mutants were rescued. However, within the inner ear, hOtx2 expression failed to rescue the lateral canal and ampulla phenotypes, and only variable rescues were observed in regions where both Otx1 and Otx2 are normally expressed. These results suggest that both Otx genes play important and differing roles in the morphogenesis of the mouse inner ear and the development of its sensory organs.