Klisch Tiemo J, Souopgui Jacob, Juergens Kathrin, Rust Barbara, Pieler Tomas, Henningfeld Kristine A
DFG-Center of Molecular Physiology of the Brain, Department of Developmental Biochemistry, University of Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen, Germany.
Dev Biol. 2006 Apr 15;292(2):470-85. doi: 10.1016/j.ydbio.2005.12.037. Epub 2006 Feb 2.
We have isolated and characterized Xenopus Mxi1, a member of the Myc/Max/Mad family of bHLHZip transcription factors. Xmxi1 transcripts are present during gastrulation and early neurula stages, earlier and in broader domains as compared to the neuronal determination factor neurogenin (X-ngnr-1). Consistent with an early role in neurogenesis, Xmxi1 is positively regulated by Sox3, SoxD, and proneural genes, as well as negatively by the Notch pathway. Loss-of-function experiments demonstrate an essential role for Xmxi1 in the establishment of a mature neural state that can be activated by factors that induce neuronal differentiation, such as SoxD and X-ngnr-1. Overexpression of Xmxi1 in Xenopus embryos results in ectopic activation of Sox3, an early pan-neural marker of proliferating neural precursor cells. Within the neural plate, the neuronal differentiation marker N-tubulin and cell cycle control genes such as XPak3 and p27(Xic1) are inhibited, but the expression of early determination and differentiation markers, including X-ngnr-1 and X-MyT1, is not affected. Inhibition of neuronal differentiation by Xmxi1 is only transient, and, at early tailbud stages, both endogenous and ectopic neurogenesis are observed. While Xmxi1 enhances cell proliferation and apoptosis in the early Xenopus embryo, both activities appear not to be required for the function of Xmxi1 in primary neurogenesis.
我们已经分离并鉴定了非洲爪蟾Mxi1，它是bHLHZip转录因子Myc/Max/Mad家族的成员。与神经元决定因子神经生成素（X-ngnr-1）相比，Xmxi1转录本在原肠胚形成期和神经胚早期阶段出现，时间更早且分布更广。与在神经发生中的早期作用一致，Xmxi1受到Sox3、SoxD和神经前体基因的正向调控，同时也受到Notch信号通路的负向调控。功能缺失实验表明，Xmxi1在建立可被诱导神经元分化的因子（如SoxD和X-ngnr-1）激活的成熟神经状态中起关键作用。在非洲爪蟾胚胎中过表达Xmxi1会导致Sox3的异位激活，Sox3是增殖神经前体细胞的早期泛神经标记物。在神经板内，神经元分化标记物N-微管蛋白以及细胞周期控制基因（如XPak3和p27(Xic1)）受到抑制，但早期决定和分化标记物（包括X-ngnr-1和X-MyT1）的表达不受影响。Xmxi1对神经元分化的抑制只是暂时的，在早期尾芽阶段，可以观察到内源性和异位神经发生。虽然Xmxi1在早期非洲爪蟾胚胎中增强了细胞增殖和凋亡，但这两种活性似乎都不是Xmxi1在初级神经发生中发挥功能所必需的。
