Changing requirements for gbx2 in development of the cerebellum and maintenance of the mid/hindbrain organizer
Changing requirements for gbx2 in development of the cerebellum and maintenance of the mid/hindbrain organizer
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DOI：
10.1016/s0896-6273(02)00935-2
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发表时间：
2002-09-26
期刊：
影响因子：
16.2
通讯作者：
Joyner, AL
中科院分区：
文献类型：
--
作者：
Li, JYH;Lao, ZM;Joyner, AL
我们检测了胚胎第9天（E9）后是否需要Gbx2来抑制小脑部位的Otx2并定位中脑/后脑组织者。与Gbx2无突变体相比，E9 （Gbx2- cko）后左homomer 1 （r1）缺乏Gbx2的小鼠存活并发育小脑。一个gbx2独立通路可以在E9后抑制r1中的Otx2。然而，中脑/后脑组织者基因的表达仍然依赖于Gbx2。我们发现Fgf8的表达通常与细胞增殖低的峡部相关，并且在Gbx2-CKO突变体中，该结构域被扩展。我们认为Fgf8通过抑制Otx2促进小脑外侧发育，同时也抑制Gbx2-CKO胚胎的小脑内侧生长。我们的工作揭示了在小脑形成过程中对Gbx2的不同需求，并为转录因子在发育过程中如何发挥多种作用提供了一个模型。
We examined whether Gbx2 is required after embryonic day 9 (E9) to repress Otx2 in the cerebellar anlage and position the midbrain/hindbrain organizer. In contrast to Gbx2 null mutants, mice lacking Gbx2 in rhombomere 1 (r1) after E9 (Gbx2-CKO) are viable and develop a cerebellum. A Gbx2-independent pathway can repress Otx2 in r1 after E9. Mid/hindbrain organizer gene expression, however, continues to be dependent on Gbx2. We found that Fgf8 expression normally correlates with the isthmus where cells undergo low proliferation and that in Gbx2-CKO mutants this domain is expanded. We propose that Fgf8 permits lateral cerebellar development through repression of Otx2 and also suppresses medial cerebellar growth in Gbx2-CKO embryos. Our work has uncovered distinct requirements for Gbx2 during cerebellum formation and provided a model for how a transcription factor can play multiple roles during development.