EXPRESSION PATTERNS OF THE E2F FAMILY OF TRANSCRIPTION FACTORS DURINGMURINE EPITHELIAL DEVELOPMENT

The E2F family of transcription factors includes five E2F and three DP forms. E2F is involved in the regulation of cell proliferation, but l ittle is known about E2F function during vertebrate development, We ha ve explored the regulation of E2F expression during mouse organogenesi s 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 e arly, undifferentiated single-cell-layer ectoderm, and later in 13.5-1 4,5-day-postcoitus (dpc) embryo epithelium, which contains several lay ers of proliferating cells, E2F-2 is up-regulated following the onset of E2F-4 expression and is first apparent in undifferentiated epitheli um at 13.5-14.5 days of gestation, In contrast, E2F-5 transcripts are detected later in gestation, once the epidermis shows evidence of stra tification, Stratification of the epidermis into basal, proliferating cells and suprabasal, terminally differentiating cells at 15.5-19.5 da ys of gestation coincides with expression of E2F-2 and E2F-4 in basal cells and of E2F-5 in suprabasal cells, Similarly, in intestinal epith elium, E2F-4 up-regulation in pseudostratified epithelium at 13.5 days of gestation precedes appearance of E2F-2 transcripts, in 14.5-dpc em bryos, in the proliferating, intervillus epithelium. In 16.5-19.5-dpc embryos, no E2F-2 transcripts were detected at the tip of the developi ng villi, which contain terminally differentiating cells, In contrast, E2F-5 transcripts were limited to the upper half of the villi and wer e absent in the intervillus epithelium. This suggests that E2F-2 and E 2F-4 may participate in maintaining epithelial cells in a proliferativ e, undifferentiated phenotype, whereas E2F-5 may be important to maint ain the differentiated state, Thus, selective regulation of E2F forms occurs during murine epithelial development, irrespective of the ectod ermal or endodermal origin of such epithelia.