Hatch Victoria L, Marin-Barba Marta, Moxon Simon, Ford Christopher T, Ward Nicole J, Tomlinson Matthew L, Desanlis Ines, Hendry Adam E, Hontelez Saartje, van Kruijsbergen Ila, Veenstra Gert Jan C, Münsterberg Andrea E, Wheeler Grant N
School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
Radboud University, Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
Dev Biol. 2016 Aug 15;416(2):361-72. doi: 10.1016/j.ydbio.2016.06.012. Epub 2016 Jun 23.
Regulation of gene expression at the level of transcriptional elongation has been shown to be important in stem cells and tumour cells, but its role in the whole animal is only now being fully explored. Neural crest cells (NCCs) are a multipotent population of cells that migrate during early development from the dorsal neural tube throughout the embryo where they differentiate into a variety of cell types including pigment cells, cranio-facial skeleton and sensory neurons. Specification of NCCs is both spatially and temporally regulated during embryonic development. Here we show that components of the transcriptional elongation regulatory machinery, CDK9 and CYCLINT1 of the P-TEFb complex, are required to regulate neural crest specification. In particular, we show that expression of the proto-oncogene c-Myc and c-Myc responsive genes are affected. Our data suggest that P-TEFb is crucial to drive expression of c-Myc, which acts as a 'gate-keeper' for the correct temporal and spatial development of the neural crest.
转录延伸水平上的基因表达调控已被证明在干细胞和肿瘤细胞中很重要，但它在整个动物体内的作用直到现在才得到充分探索。神经嵴细胞（NCCs）是一群多能细胞，在胚胎早期发育过程中从背神经管迁移到整个胚胎，在那里它们分化为多种细胞类型，包括色素细胞、颅面骨骼和感觉神经元。在胚胎发育过程中，神经嵴细胞的特化在空间和时间上都受到调控。在这里，我们表明转录延伸调控机制的组成部分，即P-TEFb复合物的CDK9和CYCLINT1，是调节神经嵴特化所必需的。特别是，我们表明原癌基因c-Myc和c-Myc反应基因的表达受到影响。我们的数据表明，P-TEFb对于驱动c-Myc的表达至关重要，而c-Myc作为神经嵴正确的时间和空间发育的“守门人”。
