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Genetic dissection of Nodal and Bmp signalling requirements during primordial germ cell development

Anna D. Senft, View ORCID ProfileElizabeth K. Bikoff, View ORCID ProfileElizabeth J. Robertson, View ORCID ProfileIta Costello
doi: https://doi.org/10.1101/464776
Anna D. Senft
Sir William Dunn School of Pathology University of Oxford Oxford OX1 3RE, UK
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Elizabeth K. Bikoff
Sir William Dunn School of Pathology University of Oxford Oxford OX1 3RE, UK
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  • ORCID record for Elizabeth K. Bikoff
Elizabeth J. Robertson
Sir William Dunn School of Pathology University of Oxford Oxford OX1 3RE, UK
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  • For correspondence: [email protected]
Ita Costello
Sir William Dunn School of Pathology University of Oxford Oxford OX1 3RE, UK
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  • ORCID record for Ita Costello
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Abstract

The essential roles played by Nodal and Bmp signalling during early mouse development have been extensively documented. Here we used 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 discovered 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. Importantly we found that beside Blimp1, down-regulated phosphoSmad159 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.

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Posted November 07, 2018.
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Genetic dissection of Nodal and Bmp signalling requirements during primordial germ cell development
Anna D. Senft, Elizabeth K. Bikoff, Elizabeth J. Robertson, Ita Costello
bioRxiv 464776; doi: https://doi.org/10.1101/464776
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Genetic dissection of Nodal and Bmp signalling requirements during primordial germ cell development
Anna D. Senft, Elizabeth K. Bikoff, Elizabeth J. Robertson, Ita Costello
bioRxiv 464776; doi: https://doi.org/10.1101/464776

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