Quantitative analysis of signaling responses during mouse primordial germ cell specification
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...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2021-05-01
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| Series: | Biology Open |
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| Online Access: | http://bio.biologists.org/content/10/5/bio058741 |
| _version_ | 1819083831501651968 |
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| author | Sophie M. Morgani Anna-Katerina Hadjantonakis |
| author_facet | Sophie M. Morgani Anna-Katerina Hadjantonakis |
| author_sort | Sophie M. Morgani |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T20:38:49Z |
| format | Article |
| id | doaj.art-3a14b8d6b18f4711a71be5eb9505e413 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-21T20:38:49Z |
| publishDate | 2021-05-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-3a14b8d6b18f4711a71be5eb9505e4132022-12-21T18:51:01ZengThe Company of BiologistsBiology Open2046-63902021-05-0110510.1242/bio.058741058741Quantitative analysis of signaling responses during mouse primordial germ cell specificationSophie M. Morgani0Anna-Katerina Hadjantonakis1 Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA 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.http://bio.biologists.org/content/10/5/bio058741bmpmapkwntmouse embryoprimordial germ cell |
| spellingShingle | Sophie M. Morgani Anna-Katerina Hadjantonakis Quantitative analysis of signaling responses during mouse primordial germ cell specification Biology Open bmp mapk wnt mouse embryo primordial germ cell |
| title | Quantitative analysis of signaling responses during mouse primordial germ cell specification |
| title_full | Quantitative analysis of signaling responses during mouse primordial germ cell specification |
| title_fullStr | Quantitative analysis of signaling responses during mouse primordial germ cell specification |
| title_full_unstemmed | Quantitative analysis of signaling responses during mouse primordial germ cell specification |
| title_short | Quantitative analysis of signaling responses during mouse primordial germ cell specification |
| title_sort | quantitative analysis of signaling responses during mouse primordial germ cell specification |
| topic | bmp mapk wnt mouse embryo primordial germ cell |
| url | http://bio.biologists.org/content/10/5/bio058741 |
| work_keys_str_mv | AT sophiemmorgani quantitativeanalysisofsignalingresponsesduringmouseprimordialgermcellspecification AT annakaterinahadjantonakis quantitativeanalysisofsignalingresponsesduringmouseprimordialgermcellspecification |