Handling Editor: John Heath
ABSTRACT
Our recent findings demonstrated that the histone chaperone and DNA repair factor aprataxin and PNK-like factor (APLF) could regulate epithelial to mesenchymal transition (EMT) during the reprogramming of murine fibroblasts and in breast cancer metastasis. Therefore, we investigated the function of APLF in EMT associated with mouse development. Here, we show that APLF is predominantly enhanced in trophectoderm (TE) and lineages derived from TE in pre- and post-implantation embryos. Downregulation of APLF induced the hatching of embryos in vitro, with a significant increase in Cdh1 and Cdx2 expression. Aplf short hairpin RNA-microinjected embryos failed to implant in vivo. Rescue experiments neutralized the knockdown effects of APLF both in vitro and in vivo. Reduced expression of Snai2 and Tead4, and the gain in Cdh1 and sFlt1 (also known as Flt1) level, marked the differentiation of APLF-knocked down trophoblast stem cells that might contribute towards the impaired implantation of embryos. Hence, our findings suggest a novel role for APLF during implantation and post-implantation development of mouse embryos. We anticipate that APLF might contribute to the establishment of maternal-fetal connection, as its fine balance is required to achieve implantation and thereby attain proper pregnancy.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: D.D.; Methodology: P.C.V., S.M.R., D.N., A.J., D.D.; Software: A.M.; Validation: P.C.V., S.M.R., D.N.; Formal analysis: P.C.V., S.M.R., D.N., A.M., D.D.; Investigation: P.C.V., S.M.R., D.N., D.D.; Resources: A.J., D.D.; Writing - original draft: P.C.V., S.M.R., D.D.; Writing - review & editing: P.C.V., A.J., A.M., D.D.; Visualization: D.D.; Supervision: D.D.; Project administration: D.D.; Funding acquisition: D.D.
Funding
This work was funded by the Department of Biotechnology, Ministry of Science of Technology (BT/PR15498/MED/12/716/2015, and partially funded by grants BT/PR17597/MED/31/335/2016 and BT/HRD/NWBA/38/10/2018); Science and Engineering Research Board (SERB), Department of Science and Technology (DST, EMR/2016/003697); and intramural funds from the institute aided by D.B.T. P.C.V. and S.M.R. are supported by DST INSPIRE fellowships (IF170833 and IF180251). Animal work carried out at the NCBS Mouse Genome Engineering Facility was partially funded by the Department of Biotechnology, Ministry of Science and Biotechnology (BT/PR5981/MED/31/181/2012;2013-2016;2018 and 102/IFD/SAN/5003/2017-2018). A.M. is supported by the Department of Biotechnology, Ministry of Science and Technology Ramalingaswami Fellowship (BT/RLF/Re-entry/03/2016) and the SERB (CRG/2018/002632).
Supplementary information
Supplementary information available online at https://jcs.biologists.org/lookup/doi/10.1242/jcs.246900.supplemental
- Received March 26, 2020.
- Accepted November 25, 2020.
- © 2021. Published by The Company of Biologists Ltd
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