The caudal limit of Otx2 expression positions the isthmic organizer
The caudal limit of Otx2 expression positions the isthmic organizer
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作者：
Broccoli, V;Boncinelli, E;Wurst, W
同源异型盒基因Otx 2在前神经管中表达，在中脑/后脑连接处（峡部组织者）有明显的限制（1）。otx 2失活实验表明，该基因对其表达结构域的发育至关重要（2）。在这里，我们调查是否尾侧限制的Otx 2表达是在定位峡部组织者和在指定中脑与后脑的命运，异位表达Otx 2在推定的前后脑使用敲入策略到En 1位点。转基因后代显示小脑共济失调。成年转基因脑的形态学和组织学研究表明，小脑前蚓部大部分缺失，而下丘互补性增大。在早期神经模式形成的中脑标志物Wnt 1和Ephrin-A5的表达，峡部组织者标志物Pax 2和FGF-8和后脑标志物Gbx 2的尾侧转移在推定的后脑领土。这些研究结果表明，尾侧限制的Otx 2的表达是足够的定位峡部组织者和编码尾侧中脑的命运内的中/后脑域。
The homeobox gene Otx2 is expressed in the anterior neural tube with a sharp limit at the midbrain/hindbrain junction (the isthmic organizer)(1). Otx2 inactivation experiments have shown that this gene is essential for the development of its expression domain(2). Here we investigate whether the caudal limit of Otx2 expression is instrumental in positioning the isthmic organizer and in specifying midbrain versus hindbrain fate, by ectopically expressing Otx2 in the presumptive anterior hindbrain using a knock-in strategy into the En1 locus. Transgenic offspring display a cerebellar ataxia. Morphological and histological studies of adult transgenic brains reveal that most of the anterior cerebellar vermis is missing whereas the inferior colliculus is complementarily enlarged. During early neural pattern formation expression of the midbrain markers Wnt1 and Ephrin-A5, the isthmic organizer markers Pax2 and Fgf-8 and the hindbrain marker Gbx2 are shifted caudally in the presumptive hindbrain territory. These findings show that the caudal limit of Otx2 expression is sufficient for positioning the isthmic organizer and encoding caudal midbrain fate within the mid/hindbrain domain.