EXPRESSION PATTERNS OF THE E2F FAMILY OF TRANSCRIPTION FACTORS DURINGMOUSE NERVOUS-SYSTEM DEVELOPMENT

The E2F family of transcription factors consists of two subgroups term ed E2F and DP. E2F is required for cell proliferation, and is necessar y for fruit fly development. E2F activity is a target for regulation b y the retinoblastoma gene family, which includes pRB, p107 and p130. M utant RB-/-, RB-/-:p107(-/-) and p107(-/-):p130(-/-) mice develop abno rmally, probably as a result of dysregulation in the activity of E2F, indicating the importance of E2F in mammalian development. To investig ate the role of E2F in murine development, we have examined the patter ns of expression of E2F-1 through E2F-5, and DP-1 in the developing ne rvous system by in situ hybridization. E2F-1, E2F-2 and E2F-5 are firs t detected in the 9.5 days post-coitus (dpc) forebrain. Expression of these E2F forms extends caudally thereafter and includes the developin g brain and the upper half of the 10.5 dpc spinal cord. By 11.5 dpc, t hese E2F factors are expressed throughout the central nervous system. In 12.5 dpc embryos, E2F-1, E2F-2 and E2F-5 are highly expressed in pr oliferating, undifferentiated neuronal precursors. As neurons differen tiate and migrate to the outer marginal zones in the nervous system, e xpression of these E2F members is extinguished. In the developing reti na, another neuronal tissue, E2F-1 expression is also confined to the proliferating, undifferentiated retinoblastic layer. In contrast, E2F- 3 expression is up-regulated as retinoblasts differentiate into the ga nglion cell layer. In non-neuronal tissues, high E2F-4 transcript leve ls are present in regions corresponding to proliferative chondrocytes, whereas E2F-2 and E2F-4 transcripts are very abundant in the thymic c ortex, which contains immature thymocytes. We conclude that individual E2F forms are differentially regulated during the development of dist inct tissues, and especially during neuronal development. (C) 1997 Els evier Science Ireland Ltd.