Expression of Pax2 and patterning of the chick inner ear
Expression of Pax2 and patterning of the chick inner ear
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DOI：
10.1023/a:1007057719025
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发表时间：
1999-10-01
期刊：
影响因子：
--
通讯作者：
Barald, KF
中科院分区：
文献类型：
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作者：
Hutson, MR;Lewis, JE;Barald, KF
耳囊肿内的早期区域化基因表达模式似乎与成熟耳结构的发育有关。在雏鸡中，转录因子Pax2在16/17期仅限于耳囊肿的背侧和整个内侧。耳囊肿的背侧区域形成内淋巴管和囊（ED/ES），耳蜗管起源于腹内侧区域。然而，在小鼠中，Pax2仅在腹内侧耳囊肿中表达，而在背耳囊肿中没有表达。Pax2缺失小鼠耳蜗缺失或截短，但前庭结构分化正常。在这里，我们证明了在小鸡中，即使新兴ED的位置相对于其环境发生了改变，无论是通过耳囊肿围绕前后轴旋转180度或将耳囊肿移植到后脑腔，新兴ED/ES也表达了高水平的Pax2。然而，在耳囊肿旋转180度后，Pax2的表达模式在耳上皮的其余部分是可塑的。Pax2在内侧（原外侧）上调，而在外侧（原内侧并表达Pax2）下调，表明Pax2的表达受环境影响。虽然在应形成耳蜗管的区域180度旋转后上皮内Pax2表达上调，但耳蜗管被截断或缺失，ED/ES出现在新的腹腹外侧位置。在耳窝或耳位早期切除后脑会改变耳囊肿中Pax2区域表达的时间。由此产生的耳囊肿和耳朵通常较小，前庭结构异常，ED/ES缺失，但耳蜗管长度正常。后脑和背脊膜间质为背耳囊肿提供了独特的营养和模式信息。我们的结果表明，ED是内耳最早的结构模式，后脑对其规范很重要。我们还表明，虽然正常的Pax2表达是耳蜗管发育所必需的，但它是腹侧耳囊肿模式事件的下游。
Early regionalized gene expression patterns within the otocyst appear to correlate with and contribute to development of mature otic structures. In the chick, the transcription factor Pax2 becomes restricted to the dorsal and entire medial side of the otocyst by stage 16/17. The dorsal region of the otocyst forms the endolymphatic duct and sac (ED/ES), and the cochlear duct is derived from the ventromedial region. In the mouse, however, Pax2 expression is reported only in the ventromedial and not the dorsal otocyst. In Pax2 null mice, the cochlea is missing or truncated, but vestibular structures differentiate normally. Here we demonstrate that in the chick, the emerging ED/ES express high levels of Pax2 even when the position of the emerging ED is altered with respect to its environment, either by 180 degrees otocyst rotations about the anterior/posterior axis or transplantation of the otocyst into the hindbrain cavity. However, the Pax2 expression pattern is plastic in the rest of the otic epithelium after 180 degrees rotation of the otocyst. Pax2 is upregulated on the medial side (formerly lateral), and downregulated on the lateral side (formerly medial and expressing Pax2) indicating that Pax2 expression is influenced by the environment. Although Pax2 is upregulated in the epithelium after 180 degrees rotations in the region that should form the cochlear duct, cochlear ducts are truncated or absent, and the ED/ES emerge in a new ventrolateral position. Ablation of the hindbrain at the placode or early otic pit stage alters the timing of regionalized Pax2 expression in the otocyst. The resulting otocysts and ears are generally smaller, vestibular structures are abnormal, ED/ES are missing but cochlear ducts are of normal length. The hindbrain and dorsal periotic mesenchyme provide unique trophic and patterning information to the dorsal otocyst. Our results demonstrate that the ED is the earliest structure patterned in the inner ear and that the hindbrain is important for its specification. We also show that, although normal Pax2 expression is required for cochlear duct development, it is downstream of ventral otocyst patterning events.