Email updates

Keep up to date with the latest news and content from BMC Developmental Biology and BioMed Central.

Open Access Research article

G1 checkpoint establishment in vivo during embryonic liver development

Xiao Qi Wang12*, Kwok Kin Chan1, Xiaoyan Ming1, Vincent CH Lui1, Randy YC Poon3, Chung Mau Lo1, Chris Norbury4 and Ronnie TP Poon12

Author Affiliations

1 Department of Surgery, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China

2 State Key Laboratory for Liver Research, The University of Hong Kong, Pokfulam, Hong Kong, China

3 Division of Life Science, University of Science & Technology, Clear Water Bay, Hong Kong, China

4 Sir William Dunn School of Pathology, University of Oxford, Oxford, UK

For all author emails, please log on.

BMC Developmental Biology 2014, 14:23  doi:10.1186/1471-213X-14-23

Published: 19 May 2014

Abstract

Background

The DNA damage-mediated cell cycle checkpoint is an essential mechanism in the DNA damage response (DDR). During embryonic development, the characteristics of cell cycle and DNA damage checkpoint evolve from an extremely short G1 cell phase and lacking G1 checkpoint to lengthening G1 phase and the establishment of the G1 checkpoint. However, the regulatory mechanisms governing these transitions are not well understood. In this study, pregnant mice were exposed to ionizing radiation (IR) to induce DNA damage at different embryonic stages; the kinetics and mechanisms of the establishment of DNA damage-mediated G1 checkpoint in embryonic liver were investigated.

Results

We found that the G2 cell cycle arrest was the first response to DNA damage in early developmental stages. Starting at E13.5/E15.5, IR mediated inhibition of the G1 to S phase transition became evident. Concomitantly, IR induced the robust expression of p21 and suppressed Cdk2/cyclin E activity, which might involve in the initiation of G1 checkpoint. The established G1 cell cycle checkpoint, in combination with an enhanced DNA repair capacity at E15.5, displayed biologically protective effects of repairing DNA double-strand breaks (DSBs) and reducing apoptosis in the short term as well as reducing chromosome deletion and breakage in the long term.

Conclusion

Our study is the first to demonstrate the establishment of the DNA damage-mediated G1 cell cycle checkpoint in liver cells during embryogenesis and its in vivo biological effects during embryonic liver development.

Keywords:
Embryonic liver; Cell cycle checkpoint; Ionizing radiation