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Quantitative analysis of signaling responses during mouse primordial germ cell specification

View ORCID ProfileSophie M. Morgani, View ORCID ProfileAnna-Katerina Hadjantonakis
doi: https://doi.org/10.1101/2021.01.11.426293
Sophie M. Morgani
1Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
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  • For correspondence: morganis@mskcc.org hadj@mskcc.org
Anna-Katerina Hadjantonakis
1Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
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  • For correspondence: morganis@mskcc.org hadj@mskcc.org
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Abstract

During early mammalian development, the pluripotent cells of the embryo are exposed to a combination of signals that drive exit from pluripotency and germ layer differentiation. At the same time, a small population of pluripotent cells give rise to the primordial germ cells (PGCs), the precursors of the sperm and egg, which pass on heritable genetic information to the next generation. Despite the importance of PGCs, it remains unclear how they are first segregated from the soma, and if this involves distinct responses to their signaling environment. To investigate this question, we mapped BMP, MAPK and WNT signaling responses over time in PGCs and their surrounding niche in vitro and in vivo at single-cell resolution. We showed that, in the mouse embryo, early PGCs exhibit lower BMP and MAPK responses compared to neighboring extraembryonic mesoderm cells, suggesting the emergence of distinct signaling regulatory mechanisms in the germline versus soma. In contrast, PGCs and somatic cells responded comparably to WNT, indicating that this signal alone is not sufficient to promote somatic differentiation. Finally, we investigated the requirement of a BMP response for these cell fate decisions. We found that cell lines with a mutation in the BMP receptor (Bmpr1a−/−), which exhibit an impaired BMP signaling response, can efficiently generate PGC-like cells revealing that canonical BMP signaling is not cell autonomously required to direct PGC-like differentiation.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted January 12, 2021.
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Quantitative analysis of signaling responses during mouse primordial germ cell specification
Sophie M. Morgani, Anna-Katerina Hadjantonakis
bioRxiv 2021.01.11.426293; doi: https://doi.org/10.1101/2021.01.11.426293
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Quantitative analysis of signaling responses during mouse primordial germ cell specification
Sophie M. Morgani, Anna-Katerina Hadjantonakis
bioRxiv 2021.01.11.426293; doi: https://doi.org/10.1101/2021.01.11.426293

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