Abstract
The essential roles played by Nodal and Bmp signalling during early mouse development have been extensively documented. Here we use conditional deletion strategies to investigate functional contributions made by Nodal, Bmp and Smad downstream effectors during primordial germ cell (PGC) development. We demonstrate that Nodal and its target gene Eomes provide early instructions during formation of the PGC lineage. We discover that Smad2 inactivation in the visceral endoderm results in increased numbers of PGCs due to an expansion of the PGC niche. Smad1 is required for specification, whereas in contrast Smad4 controls the maintenance and migration of PGCs. Additionally we find that beside Blimp1, down-regulated phospho-Smad159 levels also distinguishes PGCs from their somatic neighbours so that emerging PGCs become refractory to Bmp signalling that otherwise promotes mesodermal development in the posterior epiblast. Thus balanced Nodal/Bmp signalling cues regulate germ cell versus somatic cell fate decisions in the early posterior epiblast.
Highlights
The essential roles played by Nodal and Bmp signalling during early mouse development have been extensively documented
We found that the Smad2ΔVE embryos phenocopy the Smad2−/− embryos, strengthening the idea that the dramatic tissue disturbances observed in the null embryos predominantly reflect the loss of Smad[2] signalling in the anterior VE (AVE)
To evaluate if and when primordial germ cell (PGC) are formed in Smad2ΔVE embryos, where there is an excess of Bmp signalling, we examined PGC marker gene expression
Summary
The essential roles played by Nodal and Bmp signalling during early mouse development have been extensively documented. Smad[1] is required for specification, whereas in contrast Smad[4] controls the maintenance and migration of PGCs. we find that beside Blimp[1], down-regulated phospho-Smad[159] levels distinguishes PGCs from their somatic neighbours so that emerging PGCs become refractory to Bmp signalling that otherwise promotes mesodermal development in the posterior epiblast. Balanced Nodal/Bmp signalling cues regulate germ cell versus somatic cell fate decisions in the early posterior epiblast. Correct patterning of the early post-implantation stage embryo depends on reciprocal signalling cues by members of the TGFβ family of secreted growth factors controlling cell–cell interactions between the pluripotent epiblast and the overlying extraembryonic tissues namely the extra-embryonic ectoderm (ExE) and the visceral endoderm (VE)[9,10]. Nodal expression levels in the PS, or depleting Smad[23] in the epiblast results in failure to correctly specify the anterior definitive endoderm (DE) and the embryonic midline[14]
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