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Cell Research (2015) 25:1368-1371. www.nature.com/cr
LETTER TO THE EDITOR
Development of the anterior-posterior axis is a self-organizing process in the absence of maternal cues in the mouse embryo
Cell Research (2015) 25:1368-1371. doi:10.1038/cr.2015.104; published online 4 September 2015
Dear Editor,
Establishment of the anterior-posterior (AP) axis in the mouse embryo is crucial for proper induction of the germ layers. Despite this importance, it is unclear whether specication of the AP axis is an autonomous process or if it requires an embryonic-maternal interaction at the time of implantation. By embryonic day 5.5 (E5.5), the combined activities of Nodal, GDF3 and the Cripto co-receptor generate a proximal-distal gradient that establishes a signaling center at the distal tip of the embryo the distal visceral endoderm (DVE). This proximo-distal asymmetry is transformed into the AP axis as the DVE cells migrate. DVE cells express the Nodal antagonists, Lefty1 and Cer1, which specify the anterior identity of the underlying epiblast [1]. The expression of these key DVE markers is already triggered before implantation [2-4]. Cells that express Lefty1 and Cer1 in the late blastocyst contribute to DVE formation, together with cells that acquire de novo Cer1 and Lefty1 expression after implantation [3-5]. This pre-implantation expression of the Nodal antagonists led to the suggestion that the DVE, and therefore the AP axis, arise independently of any interaction between mother and embryo.
However, recently an alternative mechanism was proposed. By growing early post-implantation embryos in gels of different agarose concentrations Hiramatsu et al. [6] found that DVE is established only in stiffer gels, concluding that in vivo the maternal tissues should exert similar mechanical forces to enable DVE formation. Moreover, this biomechanical stress was reported to result in the transmigration of epiblast cells into the visceral endoderm (VE), which were suggested to generate the DVE at the distal tip. Therefore, two fundamentally different concepts about the mothers role in AP axis specication are currently considered.
To resolve whether establishment of the AP axis depends on mother-embryo interactions, or if it is an embryo-autonomous process, we performed a series of embryo culture and lineage tracing experiments. We used a
Cer1-GFP line, previously established as a faithful DVE reporter [6, 7], to monitor DVE formation and migration directly in living embryos.
First, we...