Sox17 is essential for proper formation of the marginal zone of extraembryonic endoderm adjacent to a developing mouse placental disk†

Abstract

In mouse conceptus, two yolk-sac membranes, the parietal endoderm (PE) and visceral endoderm (VE), are involved in protecting and nourishing early-somite-stage embryos prior to the establishment of placental circulation. Both PE and VE membranes are tightly anchored to the marginal edge of the developing placental disk, in which the extraembryonic endoderm (marginal zone endoderm: ME) shows the typical flat epithelial morphology intermediate between those of PE and VE in vivo. However, the molecular characteristics and functions of the ME in mouse placentation remain unclear. Here, we show that SOX17, not SOX7, is continuously expressed in the ME cells, whereas both SOX17 and SOX7 are coexpressed in PE cells, by at least 10.5 days postconception. The Sox17-null conceptus, but not the Sox7-null one, showed the ectopic appearance of squamous VE-like epithelial cells in the presumptive ME region, together with reduced cell density and aberrant morphology of PE cells. Such aberrant ME formation in the Sox17-null extraembryonic endoderm was not rescued by the chimeric embryo replaced with the wild-type gut endoderm by the injection of wild-type ES cells into the Sox17-null blastocyst, suggesting the cell autonomous defects in the extraembryonic endoderm of Sox17-null concepti. These findings provide direct evidence of the crucial roles of SOX17 in proper formation and maintenance of the ME region, highlighting a novel entry point to understand the in vivo VE-to-PE transition in the marginal edge of developing placenta.

Establishment of mouse stem cells that can recapitulate the developmental potential of primitive endoderm

“…The PrE lineage is vital for normal embryonic development and is the origin of the visceral endoderm (VE) of the visceral yolk sac, the parietal endoderm (PE) of the parietal yolk sac, and the marginal zone endoderm (MZE) lining the boundary between the placenta and chorionic plate of the placental disk ( 4 ). These extraembryonic endoderm tissues play crucial roles in nourishing the embryo through nutrient provision at the maternal-fetal interface ( 5 ), especially before the establishment of placental circulation [approximately embryonic day 10.5 (E10.5) in mice], in anterior-posterior patterning of the epiblast during gastrulation ( 6 ), and in yolk sac hematopoiesis ( 7 ).…”

SOX17 Is Not Required for the Derivation and Maintenance of Mouse Extraembryonic Endoderm Stem Cell Lines

“…These remaining PrE cells still have the ability to support the SOX17-null concepti to develop to E8.5 and E9.5 (Igarashi et al, 2018). The SOX17-null concepti showed high levels of GATA6 expression in PE cells at E8.5 and E9.5 (Igarashi et al, 2018). This result indicated that the model of sequential expression of PrE lineage-specific genes is Gata6 > Sox17 (Artus et al, 2010(Artus et al, , 2011.…”

“…The missing SOX17 signal reduces the number of PrE cells in blastocysts (Artus et al, 2013). These remaining PrE cells still have the ability to support the SOX17-null concepti to develop to E8.5 and E9.5 (Igarashi et al, 2018). The SOX17-null concepti showed high levels of GATA6 expression in PE cells at E8.5 and E9.5 (Igarashi et al, 2018).…”

Placental Transcriptome Adaptations to Maternal Nutrient Restriction in Sheep

“…Nine transcription factors were identified that were actually expressed in the NR placentomes that had potential to regulate at least 4 of the 22 DEGs from day 70, although none of them were expressed differently between SGA and NonSGA placentomes. Two of the transcription factors— PPARG and SOX17 —have previously identified roles in the placenta, but the rest do not [ 43 ]. PPARG is essential for placental development, has functions in adipogenesis and inflammation, and has been previously shown to be nutrient-sensitive in the sheep placenta [ 44 , 45 ].…”