Ectopic expression of dE2F and dDP induces cell proliferation and death in the Drosophila eye.

The deregulation of E2F activity is thought to contribute to the uncontrolled proliferation of many tumor cells. While the effects of overexpressing E2F genes have been studied extensively in tissue culture, the consequences of elevating E2F activity in vivo are unknown. To address this issue, transgenic lines of Drosophila were studied in which ectopic expression of dE2F and dDP was targeted to the developing eye. The co-expression of dDP or dE2F disrupted normal eye development, resulting in abnormal patterns of bristles, cone cells and photoreceptors. dE2F/dDP expression caused ectopic S phases in post-mitotic cells of the eye imaginal disc but did not disrupt the onset of neuronal differentiation. Most S phases were seen in uncommitted cells, although some cells that had initiated photo-receptor differentiation were also driven into the cell cycle. Elevated expression of dE2F and dDP caused apoptosis in the eye disc. The co-expression of baculovirus p35 protein, an inhibitor of cell death, strongly enhanced the dE2F/dDP-dependent phenotype. These results show that, in this in vivo system, the elevation of E2F activity caused post-mitotic cells to enter the cell cycle. However, these cells failed to proliferate unless rescued from apoptosis.     

Differential requirement of cyclin-dependent kinase 2 for oligodendrocyte progenitor cell proliferation and differentiation

ABSTRACT: Cyclin-dependent kinases (Cdks) and their cyclin regulatory subunits control cell growth and division. Cdk2-cyclin E complexes, phosphorylating the retinoblastoma protein, drive cells through the G1/S transition into the S phase of the cell cycle. Despite its fundamental role, Cdk2 was found to be indispensable only in specific cell types due to molecular redundancies in its function. Converging studies highlight involvement of Cdk2 and associated cell cycle regulatory proteins in oligodendrocyte progenitor cell proliferation and differentiation. Giving the contribution of this immature cell type to brain plasticity and repair in the adult, this review will explore the requirement of Cdk2 for oligodendrogenesis, oligodendrocyte progenitor cells proliferation and differentiation during physiological and pathological conditions.     

Context-dependent compensatory proliferation in epithelial homeostasis and tumorigenesis

Comment on: Warner SJ, et al. Curr Biol. 2010; In press.     

Context-dependent EEG spectral characteristics during performance of tasks

Spatial and frequency EEG characteristics of two groups of healthy adult subjects were examined in two series of experiments, which differed in conditions of the second cognitive task in a trial. The first task was the same in the two series: subjects had to evaluate size relationship between two closely spaced circles. The second task successively presented in trials of the first series consisted in the recognition of words/pseudowords, and in the second series, subjects had to localize a target letter in a matrix. It was assumed that the cognitive performance in the first series predominantly involved the ventral visual system, whereas during task performance in the second series, predominant involvement of the ventral and dorsal visual systems alternated. Multichannel EEG fragments recorded prior to the presentation of the task pairs were analyzed. Analysis of variance of the EEG spectral power revealed the generalized significant effect of the factor of the second task in the pair for delta band and lower beta subband, the power being higher in the first series. Factor brain hemisphere had a significant effect for the alpha band in the occipital area, the spectral power being lower in the left hemisphere for both experimental series. The task x hemisphere interaction was significant in the temporal cortical areas for the EEG power in alpha2 band, i.e., the predominant involvement of the ventral visual system was associated with stronger asymmetry of alpha2 rhythm and lower spectral power in this band in the left temporal area. Thus, the character of the forthcoming cognitive activity was shown to be reflected in spatio-frequency characteristics of the preceding EEG.     

E2F1 and E2F2 are differentially required for homeostasis-driven and antigen-induced T cell proliferation in vivo

Homeostasis-driven T cell proliferation occurs in response to a lymphopenic environment and is mediated by TCR and IL-7 signaling. In this report, we demonstrate a defect in the proliferation of murine naive and memory T cells lacking both E2F1 and E2F2 in response to lymphopenic conditions, suggesting that E2F1 and E2F2 function redundantly downstream of TCR and/or IL-7 signaling during homeostasis-driven proliferation. In contrast, T cell proliferation in response to antigenic stimulation is either unaffected (in vivo) or potentiated (ex vivo) by loss of E2F1 and E2F2, indicating divergent requirements for these E2F factors in T cell proliferation mediated by distinct stimuli. E2F1/E2F2 double knockout (DKO) T cells enter S phase in response to homeostatic signaling, but fail to divide, suggesting that S phase progression is either incomplete or defective. In addition, E2F1/E2F2 DKO mice do not recover normal T cell numbers following exposure to a sublethal dose of radiation, indicating that this defect in homeostasis-driven proliferation is physiologically relevant. Consistent with their failure in cell cycle progression, the differentiation of DKO T cells into memory T cells in response to homeostatic signals is significantly reduced. These observations support the idea that proliferation is required for memory T cell formation and also have implications for the development of clinical strategies to minimize the occurrence of lymphopenia-induced autoimmunity.