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Origin and role of distal visceral endoderm, a group of cells that determines anteriorposterior polarity of the mouse embryo
Katsuyoshi Takaoka1, Masamichi Yamamoto and Hiroshi Hamada1
Anteriorposterior 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 rst 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 anteriorposterior polarity is thus already determined by Lefty1+ blastomeres in the implanting blastocyst.
Vertebrates have three body axes, anteriorposterior, dorsalventral and leftright axes, and establishment of body axes is a fundamental event during early embryonic development. How and at what stage of development is the first body axis determined? Multicellular organisms seem to adopt different strategies to generate polarity. In many organisms, future body polarity is already determined before or shortly after fertilization. In Drosophila, for example, maternal determinants are asymmetrically distributed within the oocyte with respect to the future anteriorposterior polarity, and this asymmetric localization is maintained during early embryogenesis1.
In mammals, on the other hand, specification of the body axis had been thought to begin without maternal determinants, long after implantation of the embryo into the uterus. A challenging question is how the mouse embryo generates anteriorposterior polarity in the absence of maternal determinants. It has been generally accepted that anteriorposterior polarity of the mouse embryo is established when the AVE is formed at...