The Role of Trp53 in the Transcriptional Response to Ionizing Radiation in the Developing Brain
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The Role of Trp53 in the Transcriptional Response to Ionizing Radiation in the Developing Brain. / Verheyde, Joris; de Saint-Georges, Louis; Leyns, Luc; Benotmane, Rafi; Mergeay, Max (Peer reviewer).
In: DNA Research, Vol. 13, No. 2, 21.03.2006, p. 65-75.Research output: Contribution to journal › Article › peer-review
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T1 - The Role of Trp53 in the Transcriptional Response to Ionizing Radiation in the Developing Brain
AU - Verheyde, Joris
AU - de Saint-Georges, Louis
AU - Leyns, Luc
AU - Benotmane, Rafi
A2 - Mergeay, Max
N1 - Score = 10
PY - 2006/3/21
Y1 - 2006/3/21
N2 - Brain formation results from a series of well-timed consecutive waves of cellular proliferation, migration and differentiation. Acute irradiation during pregnancy selectively interferes with these events to result in malformations such as microcephaly, reduced cortical thickness and mental retardation. In the present study we performed a straight-through cDNA-microarray analysis of the developing mouse brain at embryonic day E13, 3 h after in utero exposure to 50 cGy X-radiation. This dataset was used as an indication of genes involved in different pathways that are activated upon early radiation exposure, and for further evaluation using quantitative PCR (qPCR). Microarray and qPCR data revealed that the main activated pathways in irradiated wild-type embryos are involved in the regulation of a p53-mediated pathway that may lead to cell cycle delay/arrest and increased levels of apoptosis. To define whether the transcriptional radiation response was solely p53 mediated, we analysed the expression of cell cycle regulating genes in a Trp53 null mutant. The modulated expression of cell cycle regulating genes such as cyclins and Cdk genes indicated the induction of a cell cycle arrest, without evidence for the onset of apoptosis. ABSTRACT TRUNCATED AT 200 WORDS.
AB - Brain formation results from a series of well-timed consecutive waves of cellular proliferation, migration and differentiation. Acute irradiation during pregnancy selectively interferes with these events to result in malformations such as microcephaly, reduced cortical thickness and mental retardation. In the present study we performed a straight-through cDNA-microarray analysis of the developing mouse brain at embryonic day E13, 3 h after in utero exposure to 50 cGy X-radiation. This dataset was used as an indication of genes involved in different pathways that are activated upon early radiation exposure, and for further evaluation using quantitative PCR (qPCR). Microarray and qPCR data revealed that the main activated pathways in irradiated wild-type embryos are involved in the regulation of a p53-mediated pathway that may lead to cell cycle delay/arrest and increased levels of apoptosis. To define whether the transcriptional radiation response was solely p53 mediated, we analysed the expression of cell cycle regulating genes in a Trp53 null mutant. The modulated expression of cell cycle regulating genes such as cyclins and Cdk genes indicated the induction of a cell cycle arrest, without evidence for the onset of apoptosis. ABSTRACT TRUNCATED AT 200 WORDS.
KW - cDNA microarray
KW - ionizing radiation
KW - brain development
KW - Trp53
KW - p53
UR - http://ecm.sckcen.be/OTCS/llisapi.dll/open/ezp_30511
UR - http://knowledgecentre.sckcen.be/so2/bibref/3521
U2 - 10.1093/dnares/dsi028
DO - 10.1093/dnares/dsi028
M3 - Article
VL - 13
SP - 65
EP - 75
JO - DNA Research
JF - DNA Research
SN - 1340-2838
IS - 2
ER -
ID: 315156