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Published on: October 27, 2008
Nodal antagonists in the anterior visceral endoderm prevent the formation of multiple primitive streaks
Aitana Perea-Gomez1, Francis D J Vella, William Shawlot
1IGBMC/CNRS/INSERM, Université Louis Pasteur, 67404 Illkirch cedex, CU de, Strasbourg, France.
Abstract:
The anterior visceral endoderm plays a pivotal role in establishing anterior-posterior polarity of the mouse embryo, but the molecular nature of the signals required remains to be determined. Here, we demonstrate that Cerberus-like(-/-);Lefty1(-/-) compound mutants can develop a primitive streak ectopically in the embryo. This defect is not rescued in chimeras containing wild-type embryonic, and Cerberus-like(-/-);Lefty1(-/-) extraembryonic, cells but is rescued in Cerberus-like(-/-); Lefty1(-/-) embryos after removal of one copy of the Nodal gene. Our findings provide support for a model whereby Cerberus-like and Lefty1 in the anterior visceral endoderm restrict primitive streak formation to the posterior end of mouse embryos by antagonizing Nodal signaling. Both antagonists are also required for proper patterning of the primitive streak.
Insights
The anterior visceral endoderm uses Cerberus-like and Lefty1 to block Nodal signaling, preventing ectopic primitive streak formation in mouse embryos. These factors are crucial for correct embryo patterning and polarity establishment.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- The anterior visceral endoderm (AVE) is critical for establishing anterior-posterior (A-P) polarity in mouse embryos.
- The specific molecular signals mediating AVE function in A-P patterning are not fully understood.
Purpose of the Study:
- To investigate the roles of Cerberus-like and Lefty1 in mouse embryonic polarity and primitive streak formation.
- To elucidate the molecular mechanisms by which AVE signals regulate early embryonic patterning.
Main Methods:
- Generation and analysis of Cerberus-like(-/-);Lefty1(-/-) compound mutant mouse embryos.
- Construction and analysis of embryonic chimeras.
- Genetic manipulation involving Nodal gene dosage.
Main Results:
- Cerberus-like(-/-);Lefty1(-/-) mutants exhibit ectopic primitive streak formation.
- This defect is not rescued by wild-type embryonic or mutant extraembryonic cells in chimeras.
- The defect is rescued in compound mutants by reducing Nodal gene dosage.
- Cerberus-like and Lefty1 are essential for proper primitive streak patterning.
Conclusions:
- Cerberus-like and Lefty1 act antagonistically to Nodal signaling in the AVE to restrict primitive streak formation to the posterior pole.
- These antagonists are indispensable for correct primitive streak development and overall embryonic patterning.
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