Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.26.171132v1?rss=1 Authors: Mbouombouo Mfossa, A. C., Verslegers, M., Verreet, T., Fida, H. B., Mysara, M., van IJcken, W., De Vos, W. H., Moons, L., Baatout, S., Benotmane, M. A., Huylebroeck, D., Quintens, R. Abstract: p53 regulates the cellular DNA damage response (DDR). Hyperactivation of p53 during embryonic development, however, can lead to a range of developmental defects including microcephaly. Here, we induce microcephaly by acute irradiation of mouse fetuses at the onset of neurogenesis. Besides a classical DDR culminating in massive apoptosis, we observe ectopic neurons in the subventricular zone in the brains of irradiated mice, indicative of premature neuronal differentiation. A transcriptomic study indicates that p53 activates both DDR genes and differentiation-associated genes. In line with this, mice with a targeted inactivation of Trp53 in the dorsal forebrain, do not show this ectopic phenotype and partially restore brain size after irradiation. Irradiation furthermore induces an epithelial-to-mesenchymal transition-like process resembling the radiation-induced proneural-mesenchymal transition in glioma and glioma stem-like cells. Our results demonstrate a critical role for p53 beyond the DDR as a regulator of neural progenitor cell fate in response to DNA damage. Copy rights belong to original authors. Visit the link for more info