McIlvain Vera A, Knox Barry E
Department of Biochemistry & Molecular Biology and Ophthalmology, SUNY Upstate Medical University, Syracuse, New York 13210, USA.
Dev Dyn. 2007 Jul;236(7):1970-9. doi: 10.1002/dvdy.21128.
Transformation of undifferentiated progenitors into specific cell types is largely dependent on temporal and spatial expression of a complex network of transcription factors. Here, we examined whether neural retina leucine zipper (Nrl) and photoreceptor-specific nuclear receptor Nr2e3 transcription factors contribute to cell fate determination. We cloned the Xenopus Nr2e3 gene and showed that its temporal and spatial expression is similar to its mammalian ortholog. We tested its in vivo function by misexpressing these transcription factors in Xenopus eye primordia, demonstrating that either human Nr2e3 or Nrl directed photoreceptor precursors to become rods at the expense of cones. Furthermore, overexpression of Xenopus Nrl dramatically increased the number of lens fibers, whereas human Nrl did not, suggesting evolutionary divergence of function of the Nrl gene family. Misexpression of Nrl and Nr2e3 together were more effective than either transcription factor alone in directing precursors to the rod fate.
未分化祖细胞向特定细胞类型的转变在很大程度上依赖于转录因子复杂网络的时空表达。在此，我们研究了神经视网膜亮氨酸拉链（Nrl）和光感受器特异性核受体Nr2e3转录因子是否有助于细胞命运的决定。我们克隆了非洲爪蟾的Nr2e3基因，并表明其时空表达与其哺乳动物直系同源基因相似。我们通过在非洲爪蟾眼原基中错误表达这些转录因子来测试其体内功能，证明人类Nr2e3或Nrl均可引导光感受器前体细胞变成视杆细胞，而以视锥细胞为代价。此外，非洲爪蟾Nrl的过表达显著增加了晶状体纤维的数量，而人类Nrl则没有，这表明Nrl基因家族功能存在进化差异。Nrl和Nr2e3共同错误表达在引导前体细胞走向视杆细胞命运方面比单独任何一种转录因子都更有效。
