Gene silencing of tead3 abrogates radiation-induced adaptive response in cultured mouse limb bud cells

Abstract

There is a crucial need to better understand the effects of low-doses of ionizing radiation in fetal models. Radiation-induced adaptive response (AR) was described in mouse embryos pre-exposed in utero to low-doses of X-rays, which exhibited lower apoptotic levels in the limb bud. We previously described AR-specific gene modulations in the mouse embryo. In this study, we evaluated the role of three candidate genes in the apoptotic AR in a micromass culture of limb bud cells: Csf1, Cacna1a and Tead3. Gene silencing of these three genes abrogated AR. Knowing that TEAD3 protein levels are significantly higher in adapted cells and that YAP/TAZ/TEAD are involved in the control of cell proliferation and apoptosis, we suggest that modulation of Tead3 could play a role in the induction of AR in our model, seen as a reduction of radiation-induced apoptosis and a stimulation of proliferation and differentiation in limb bud cells.