Dagnino L, Fry C J, Bartley S M, Farnham P, Gallie B L, Phillips R A
Division of Immunology and Cancer Research, Hospital for Sick Children, University of Toronto, Ontario, Canada.
Cell Growth Differ. 1997 May;8(5):553-63.
The E2F family of transcription factors includes five E2F and three DP forms. E2F is involved in the regulation of cell proliferation, but little is known about E2F function during vertebrate development. We have explored the regulation of E2F expression during mouse organogenesis by in situ hybridization. We find selective up-regulation of E2F-2, E2F-4, and E2F-5 transcripts in epidermis and intestinal epithelium at important developmental stages. E2F-4 transcript levels are high in early, undifferentiated single-cell-layer ectoderm, and later in 13.5-14.5-day-postcoitus (dpc) embryo epithelium, which contains several layers of proliferating cells. E2F-2 is up-regulated following the onset of E2F-4 expression and is first apparent in undifferentiated epithelium at 13.5-14.5 days of gestation. In contrast, E2F-5 transcripts are detected later in gestation, once the epidermis shows evidence of stratification. Stratification of the epidermis into basal, proliferating cells and suprabasal, terminally differentiating cells at 15.5-19.5 days of gestation coincides with expression of E2F-2 and E2F-4 in basal cells and of E2F-5 in suprabasal cells. Similarly, in intestinal epithelium, E2F-4 up-regulation in pseudostratified epithelium at 13.5 days of gestation precedes appearance of E2F-2 transcripts, in 14.5-dpc embryos, in the proliferating, intervillus epithelium. In 16.5-19.5-dpc embryos, no E2F-2 transcripts were detected at the tip of the developing villi, which contain terminally differentiating cells. In contrast, E2F-5 transcripts were limited to the upper half of the villi and were absent in the intervillus epithelium. This suggests that E2F-2 and E2F-4 may participate in maintaining epithelial cells in a proliferative, undifferentiated phenotype, whereas E2F-5 may be important to maintain the differentiated state. Thus, selective regulation of E2F forms occurs during murine epithelial development, irrespective of the ectodermal or endodermal origin of such epithelia.
转录因子E2F家族包括五种E2F和三种DP形式。E2F参与细胞增殖的调控，但在脊椎动物发育过程中E2F的功能却知之甚少。我们通过原位杂交研究了小鼠器官发生过程中E2F表达的调控。我们发现在重要的发育阶段，表皮和肠上皮中E2F-2、E2F-4和E2F-5转录本有选择性上调。E2F-4转录本水平在早期未分化的单细胞层外胚层中较高，在妊娠13.5 - 14.5天（dpc）的胚胎上皮中也较高，该上皮含有几层增殖细胞。E2F-2在E2F-4表达开始后上调，首次在妊娠13.5 - 14.5天的未分化上皮中明显可见。相比之下，E2F-5转录本在妊娠后期才被检测到，此时表皮出现分层迹象。妊娠15.5 - 19.5天时，表皮分层为基底增殖细胞和基底上层终末分化细胞，这与基底细胞中E2F-2和E2F-4的表达以及基底上层细胞中E2F-5的表达一致。同样，在肠上皮中，妊娠13.5天时假复层上皮中E2F-4的上调先于E2F-2转录本在妊娠14.5天的胚胎中增殖的绒毛间上皮中出现。在妊娠16.5 - 19.5天的胚胎中，在含有终末分化细胞的发育绒毛尖端未检测到E2F-2转录本。相比之下，E2F-5转录本仅限于绒毛的上半部分，在绒毛间上皮中不存在。这表明E2F-2和E2F-4可能参与维持上皮细胞的增殖、未分化表型，而E2F-5对于维持分化状态可能很重要。因此，在小鼠上皮发育过程中会发生E2F形式的选择性调控，而不考虑此类上皮的外胚层或内胚层起源。
