Abstract
Anterior–posterior polarity of the mouse embryo has been thought to be established when distal visceral endoderm (DVE) at embryonic day (E) 5.5 migrates toward the future anterior side to form anterior visceral endoderm (AVE). Lefty1, a marker of DVE and AVE, is asymmetrically expressed in implanting mouse embryos. We now show that Lefty1 is expressed first in a subset of epiblast progenitor cells and then in a subset of primitive endoderm progenitors. Genetic fate mapping indicated that the latter cells are destined to become DVE. In contrast to the accepted notion, however, AVE is not derived from DVE but is newly formed after E5.5 from Lefty1− visceral endoderm cells that move to the distal tip. Concomitant with DVE migration, all visceral endoderm cells in the embryonic region undergo global movement. In embryos subjected to genetic ablation of Lefty1-expressing DVE cells, AVE was formed de novo but the visceral endoderm including the newly formed AVE failed to migrate, indicating that DVE guides the migration of AVE by initiating the global movement of visceral endoderm cells. Future anterior–posterior polarity is thus already determined by Lefty1+ blastomeres in the implanting blastocyst.
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Acknowledgements
We thank A. Fukumoto, H. Nishimura, K. Miyama, Y. Hamada, S. Ohishi, and K. Yamashita for technical assistance, A. Miyawaki for the mVenus complementary DNA and R. Tsien for tdTomato and Cherry cDNAs. This work was supported by a grant from CREST (Core Research for Evolutional Science and Technology) of the Japan Science and Technology Corporation as well as by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. K.T. was supported by a fellowship from the Japan Society for the Promotion of Science for Japanese Junior Scientists and Grant-in-Aid for Scientific Research on Innovative Areas.
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Project planning was carried out mainly by K.T. and partly by M.Y. and H.H.; all experiments involving mouse embryos were carried out by K.T.; the manuscript was written by K.T. and H.H.
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Takaoka, K., Yamamoto, M. & Hamada, H. Origin and role of distal visceral endoderm, a group of cells that determines anterior–posterior polarity of the mouse embryo. Nat Cell Biol 13, 743–752 (2011). https://doi.org/10.1038/ncb2251
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DOI: https://doi.org/10.1038/ncb2251
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