Koyano-Nakagawa N, Kim J, Anderson D, Kintner C
The Salk Institute for Biological Studies, PO Box 85800, La Jolla, CA 92186-5800, USA.
Development. 2000 Oct;127(19):4203-16. doi: 10.1242/dev.127.19.4203.
During the development of the vertebrate nervous system, neurogenesis is promoted by proneural bHLH proteins such as the neurogenins, which act as potent transcriptional activators of neuronal differentiation genes. The pattern by which these proteins promote neuronal differentiation is thought to be governed by inhibitors, including a class of transcriptional repressors called the WRPW-bHLH proteins, which are similar to Drosophila proteins encoded by hairy and genes in the enhancer of split complex (E-(SPL)-C). Here, we describe the isolation and characterization of Hes6, which encodes a novel WRPW-bHLH protein expressed during neurogenesis in mouse and Xenopus embryos. We show that Hes6 expression follows that of neurogenins but precedes that of the neuronal differentiation genes. We provide several lines of evidence to show that Hes6 expression occurs in developing neurons and is induced by the proneural bHLH proteins but not by the Notch pathway. When ectopically expressed in Xenopus embryos, Hes6 promotes neurogenesis. The properties of Hes6 distinguish it from other members of the WRPW-bHLH family in vertebrates, and suggest that it acts in a positive-feedback loop with the proneural bHLH proteins to promote neuronal differentiation.
在脊椎动物神经系统发育过程中，神经发生由神经原蛋白等原神经bHLH蛋白促进，这些蛋白作为神经元分化基因的强效转录激活因子发挥作用。这些蛋白促进神经元分化的模式被认为受抑制剂调控，包括一类称为WRPW-bHLH蛋白的转录抑制因子，它们类似于果蝇中由毛状基因和分裂复合物增强子（E-(SPL)-C）中的基因编码的蛋白。在此，我们描述了Hes6的分离和特性，它编码一种在小鼠和非洲爪蟾胚胎神经发生期间表达的新型WRPW-bHLH蛋白。我们表明，Hes6的表达跟随神经原蛋白的表达，但先于神经元分化基因的表达。我们提供了几条证据表明，Hes6在发育中的神经元中表达，并由原神经bHLH蛋白诱导，但不由Notch途径诱导。当在非洲爪蟾胚胎中异位表达时，Hes6促进神经发生。Hes6的特性使其有别于脊椎动物中WRPW-bHLH家族的其他成员，并表明它与原神经bHLH蛋白在正反馈回路中发挥作用以促进神经元分化。
