Amnion formation in the mouse embryo: the single amniochorionic fold model

Abstract

BackgroundDespite the detailed knowledge obtained over the last decade on the molecular regulation of gastrulation in amniotes, the process of amnion development has been poorly described and illustrated in mice, and conflicting descriptions exist. Understanding the morphogenesis and development not only of the early mouse embryo, but also of its extraembryonic tissues, is crucial for correctly interpreting fate-mapping data and mouse mutants with gastrulation defects. Moreover, the recent isolation from amnion of cells with stem cell features further argues for a better understanding of the process of amnion formation. Here, we revisit the highly dynamic process of amnion formation in the mouse. Amnion development starts early during gastrulation and is intimately related to the formation of the exocoelom and the expansion of the amniotic fold. The authoritative description involves the fusion of two amniotic folds, a big posterior and a smaller anterior fold. We challenged this 'two amniotic folds' model by performing detailed histomorphological analyses of dissected, staged embryos and 3D reconstructions using historical sections.ResultsA posterior fold of extraembryonic ectoderm and associated epiblast is formed early during gastrulation by accumulation of extraembryonic mesoderm posterior to the primitive streak. Previously called the "posterior amniotic fold", we rename it the "amniochorionic fold" (ACF) because it forms both amnion and chorion. Exocoelom formation within the ACF seems not to involve apoptosis within the mesoderm. The ACF and exocoelom expand without disrupting the anterior junction of epiblast, extraembryonic ectoderm and visceral endoderm. No separate anterior fold is formed; its absence was confirmed in 3D reconstructions. Amnion and chorion closure is eccentric, close to the anterior margin of the egg cylinder: we name it the "anterior separation point".ConclusionsHere, we reconcile previous descriptions of amnion formation and provide new nomenclature, as well as an animation, that clarify and emphasize the arrangement of the tissues that contribute to amnion development and the dynamics of the process. According to our data, the amnion and the chorion are formed by a single amniochorionic fold initiated posteriorly. Finally, we give an overview on mutant mouse models with impaired amnion development.

Essential role of the CUL4B ubiquitin ligase in extra-embryonic tissue development during mouse embryogenesis

“…In contrast, CUL4A levels were ubiquitously low throughout the embryo ( Figure 4G and 4H). At E7.5, CUL4B was mainly detected in the chorionic membrane (Figure 4Ja, arrowhead), which originates partially from the extra-embryonic ectoderm [26]. CUL4B was also detected at high levels in the neuroectoderm (Figure 4Jb, arrow), and at lower levels in other extra-embryonic tissues (Figure 4Jc).…”

Pervasive polymorphic imprinted methylation in the human placenta

“…In mouse and, likely, in human, chorion is derived from both the TE and extraembryonic mesoderm (Downs 2011;Pereira et al 2011), while molecular data in human suggest that there may also be a later contribution from epiblast, prior to primitive streak formation at day 15, to both chorion and amnion (Robinson et al 2002;Penaherrera et al 2012). The relative loss of DNA methylation observed in chorion and amnion compared to placental villi suggests that imprinting at placental-specific DMRs in the embryonic lineages has already begun to be lost at the time of primitive streak formation (Fig.…”

Antagonism of Nodal signaling by BMP/Smad5 prevents ectopic primitive streak formation in the mouse amnion

“…Amnion closure is delayed in the Smad5 mutant, which resembles a milder phenotype of the Bmp2 mutant mice (Zhang and Bradley, 1996). The amnion is normally a thin and avascular extra-embryonic tissue that forms from a single amniochorionic fold during gastrulation and ultimately surrounds and cushions the fetus (Pereira et al, 2011). After amnion closure, the Smad5 mutant amnion develops specific defects that cannot be attributed to reduced BMP signaling (Bosman et al, 2006).…”