Origin and role of distal visceral endoderm, a group of cells that determines anterior-posterior polarity of the mouse embryo
Origin and role of distal visceral endoderm, a group of cells that determines anterior-posterior polarity of the mouse embryo
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DOI：
10.1038/ncb2251
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发表时间：
2011-07-01
影响因子：
21.3
通讯作者：
Hamada, Hiroshi
中科院分区：
文献类型：
--
作者：
Takaoka, Katsuyoshi;Yamamoto, Masamichi;Hamada, Hiroshi
小鼠胚胎的前后极性被认为是在胚胎日(E) 5.5时远端内脏内胚层（DVE）向未来的前侧迁移形成前内脏内胚层（AVE）时建立的。Lefty1是DVE和AVE的标记物，在小鼠胚胎中对称表达。我们现在发现Lefty1首先在外胚层祖细胞的一个亚群中表达，然后在原始内胚层祖细胞的一个亚群中表达。遗传命运图谱表明，后一种细胞注定成为DVE。然而，与公认的观点相反，AVE并非来源于DVE，而是在E5.5之后由Lefty1（-）内脏内胚层细胞向远端移动而新形成的。随着DVE的迁移，胚胎区所有内脏内胚层细胞都进行全局运动。在基因消融表达lefty1的DVE细胞的胚胎中，AVE重新形成，但包括新形成的AVE在内的内脏内胚层未能迁移，这表明DVE通过启动内脏内胚层细胞的全局运动来引导AVE的迁移。因此，未来的前后极性已经由着床囊胚中的Lefty1（+）卵裂球决定。
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 a symmetrically 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.