title: Identification of novel radiation-induced p53-dependent transcripts extensively regulated during mouse brain development.
abstract: Ionizing radiation is a potent activator of the tumor suppressor gene p53, which itself regulates the transcription of genes involved in canonical pathways such as the cell cycle, DNA repair and apoptosis as well as other biological processes like metabolism, autophagy, differentiation and development. In this study, we performed a meta-analysis on gene expression data from different in vivo and in vitro experiments to identify a signature of early radiation-responsive genes which were predicted to be predominantly regulated by p53. Moreover, we found that several genes expressed different transcript isoforms after irradiation in a p53-dependent manner. Among this gene signature, we identified novel p53 targets, some of which have not yet been functionally characterized. Surprisingly, in contrast to genes from the canonical p53-regulated pathways, our gene signature was found to be highly enriched during embryonic and post-natal brain development and during in vitro neuronal differentiation. Furthermore, we could show that for a number of genes, radiation-responsive transcript variants were upregulated during development and differentiation, while radiation non-responsive variants were not. This suggests that radiation exposure of the developing brain and immature cortical neurons results in the p53-mediated activation of a neuronal differentiation program. Overall, our results further increase the knowledge of the radiation-induced p53 network of the embryonic brain and provide more evidence concerning the importance of p53 and its transcriptional targets during mouse brain development.
authors: Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, B-2400 Mol, Belgium roel.quintens@sckcen.be.
authors: Roel
authors: R
authors: Quintens
authors: Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, B-2400 Mol, Belgium Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, B-3000 Leuven, Belgium.
authors: Tine
authors: T
authors: Verreet
authors: Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, B-2400 Mol, Belgium.
authors: Ann
authors: A
authors: Janssen
authors: Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, B-2400 Mol, Belgium.
authors: Mieke
authors: M
authors: Neefs
authors: Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, B-2400 Mol, Belgium.
authors: Liselotte
authors: L
authors: Leysen
authors: Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, B-2400 Mol, Belgium.
authors: Arlette
authors: A
authors: Michaux
authors: Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, B-2400 Mol, Belgium.
authors: Mieke
authors: M
authors: Verslegers
authors: Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, B-2400 Mol, Belgium.
authors: Nada
authors: N
authors: Samari
authors: Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, B-2400 Mol, Belgium Present address: Nutritional Biochemistry and Space Biology Lab, Department of Pharmacology and Bio-molecular Sciences, Università degli Studi di Milano, 20122 Milano, Italy.
authors: Giuseppe
authors: G
authors: Pani
authors: Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, B-2400 Mol, Belgium.
authors: Joris
authors: J
authors: Verheyde
authors: Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, B-2400 Mol, Belgium Cell Systems and Imaging Research Group (CSI), Department of Molecular Biotechnology, Ghent University, B-9000 Ghent, Belgium.
authors: Sarah
authors: S
authors: Baatout
authors: Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, B-2400 Mol, Belgium.
authors: Mohammed A
authors: MA
authors: Benotmane
keywords: Alternative splicing; Development; Embryonic brain; Ionizing radiation; Neuronal differentiation; p53 targets