Histone Chaperone APLF Level Dictate Implantation of Mouse Embryo

Abstract

Our recent findings demonstrated that histone chaperone and DNA repair factor Aprataxin PNK like factor (APLF) could regulate Epithelial to mesenchymal transition (EMT), during reprogramming of murine fibroblast and in breast cancer metastasis. EMT constitutes the first cellular transition during development as well. So, we investigated the function of APLF in mouse development. Here we show that APLF is predominantly restricted to trophectoderm and lineages derived from trophectoderm in pre and post implantation embryos. shRNA mediated downregulation of APLF induced hatching of embryos in vitro with significant increase in Ecadherin (Cdh1) and Cdx2 expression. Aplf shRNA microinjected embryos failed to implant in vitro. Rescue experiments neutralized the - knockdown effects of APLF both in vitro and in vivo. Significant reduction in Snai2, Tead4 while gain in Cdh1, Cdx2 and sFlt1 level marked inhibition of EMT in differentiating APLF knocked down Trophoblast Stem Cells. We predict that elevated level of Cdh1/Cdx2/sFlt1 upon APLF-downregulation might contribute towards the impaired implantation of embryos. Hence, our findings suggest a novel role of APLF in implantation and in the post-implantation development of mouse embryo. We anticipate that APLF might contribute in the establishment of maternal-fetal connection, as its fine balance is required to achieve implantation and thereby attain proper pregnancy.