Upregulation of E2F1 in cerebellar neuroprogenitor cells and cell cycle arrest during postnatal brain development

Upregulation of E2F1 in cerebellar neuroprogenitor cells and cell cycle arrest during postnatal brain development

Author Suzuki, Daniela E. Autor UNIFESP Google Scholar
Ariza, Carolina B. Autor UNIFESP Google Scholar
Porcionatto, Marimelia A. Autor UNIFESP Google Scholar
Okamoto, Oswaldo Keith Autor UNIFESP Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Abstract In the developing cerebellum, proliferation of granular neuroprogenitor (GNP) cells lasts until the early postnatal stages when terminal maturation of the cerebellar cortex occurs. GNPs are considered cell targets for neoplastic transformation, and disturbances in cerebellar GNP cell proliferation may contribute to the development of pediatric medulloblastoma. At the molecular level, proliferation of GNPs is regulated through an orchestrated action of the SHH, NOTCH, and WNT pathways, but the underlying mechanisms still need to be dissected. Here, we report that expression of the E2F1 transcription factor in rat GNPs is inversely correlated with cell proliferation rate during postnatal development, as opposed to its traditional SHH-dependent induction of cell cycle. Proliferation of GNPs peaked at postnatal day 3 (P3), with a subsequent continuing decrease in proliferation rates occurring until P12. Such gradual decline in proliferating neuroprogenitors paralleled the extent of cerebellum maturation confirmed by histological analysis with cresyl violet staining and temporal expression profiling of SHH, NOTCH2, and WNT4 genes. A time course analysis of E2F1 expression in GNPs revealed significantly increased levels at P12, correlating with decreased cell proliferation. Expression of the cell cycle inhibitor p18 (Ink4c) , a target of E2F1, was also significantly higher at P12. Conversely, increased E2F1 expression did not correlate with either SMAC/DIABLO and BCL2 expression profiles or apoptosis of cerebellar cells. Altogether, these results suggest that E2F1 may also be involved in the inhibition of GNP proliferation during rat postnatal development despite its conventional mitogenic effects.
Keywords Gene expression
Neuroprogenitors
Cellular proliferation
Central nervous system
Development
Transcription factor
E2F1
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
INCT-CETGEN
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Date 2011-08-01
Published in In Vitro Cellular & Developmental Biology-animal. New York: Springer, v. 47, n. 7, p. 492-499, 2011.
ISSN 1071-2690 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 492-499
Origin http://dx.doi.org/10.1007/s11626-011-9426-3
Access rights Closed access
Type Article
Web of Science ID WOS:000293136800012
URI http://repositorio.unifesp.br/handle/11600/33920

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