Xenopus Nkx6.1 and Nkx6.2 are required for mid-hindbrain boundary development
Xenopus Nkx6.1 and Nkx6.2 are required for mid-hindbrain boundary development
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DOI：
10.1007/s00427-013-0437-9
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发表时间：
2013-07-01
影响因子：
2.4
通讯作者：
Mao, Bingyu
中科院分区：
文献类型：
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作者：
Ma, Pengcheng;Xia, Yingjie;Mao, Bingyu
中脑-后脑边界（MHB）组织者是脊椎动物中脑和小脑模式化的最佳研究的局部组织者之一，并由几种转录因子和信号（包括Wnt信号）的调控网络建立。在本研究中，我们发现，非洲爪蟾Nkx6.1和Nkx6.2，两个转录因子的Nkx同源框家庭，所需的MHB的形成。在非洲爪蟾胚胎中，nkx6.1和nkx6.2在MHB中表达，通过特定的吗啉代敲低nkx6.1或nkx6.2会破坏en 2和wnt 1的MHB表达，wnt 1是脊椎动物MHB形成的关键调节因子。在nkx6.1/nkx6.2 morphants中，共同注射wnt 1或dngsk 3 β mRNA，激活Wnt信号传导，挽救en 2的表达。Nkx6.1和Nkx6.2在培养的哺乳动物细胞和非洲爪蟾胚胎中的报告基因测定中激活经典Wnt信号传导。抑制野生型Nkx6.2激活Wnt信号传导的能力的Nkx6.2缺失构建体也降低了非洲爪蟾胚胎中en 2的MHB表达。这些结果表明，Nkx6.1和Nkx6.2参与非洲爪蟾胚胎MHB的形成，可能通过调节wnt 1的表达。
The mid-hindbrain boundary (MHB) organizer is among the best studied local organizers that patterns the midbrain and cerebellum in vertebrates and is established by a regulatory network of several transcription factors and signals, including Wnt signaling. In the present study, we found that Xenopus Nkx6.1 and Nkx6.2, two transcription factors of the Nkx homeobox family, are required for MHB formation. In Xenopus embryos, nkx6.1 and nkx6.2 are expressed in the MHB, and knockdown of either nkx6.1 or nkx6.2 by specific morpholinos disrupts the MHB expression of en2 as well as wnt1, a key regulator for vertebrate MHB formation. In the nkx6.1/nkx6.2 morphants, co-injection of wnt1 or dngsk3 beta mRNA, which activates Wnt signaling, rescues the expression of en2. Nkx6.1 and Nkx6.2 activate canonical Wnt signaling in reporter assays in both cultured mammalian cells and Xenopus embryos. An Nkx6.2 deletion construct, which inhibits the ability of wild type Nkx6.2 to activate Wnt signaling, also reduces the MHB expression of en2 in Xenopus embryos. These results suggest that Nkx6.1 and Nkx6.2 are involved in MHB formation in Xenopus embryos, likely by modulating wnt1 expression.