Gene silencing of Tead3 abrogates radiation-induced adaptive response in cultured mouse limb bud cells

J Radiat Res. 2011;52(1):39-46. doi: 10.1269/jrr.10101.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / physiology
  • Adaptation, Physiological / radiation effects
  • Animals
  • Apoptosis / drug effects*
  • Cells, Cultured
  • Dose-Response Relationship, Radiation
  • Gene Silencing / physiology
  • Limb Buds / cytology*
  • Limb Buds / physiology*
  • Limb Buds / radiation effects
  • Mice
  • Mice, Inbred ICR
  • Radiation Tolerance / physiology*
  • Radiation Tolerance / radiation effects
  • TEA Domain Transcription Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • TEA Domain Transcription Factors
  • Tead3 protein, mouse
  • Transcription Factors