The Apical Domain Is Required and Sufficient for the First Lineage Segregation in the Mouse Embryo.
Mammalian development begins with segregation of the extra-embryonic trophectoderm from the embryonic lineage in the blastocyst. While cell polarity and adhesion play key roles, the decisive cue driving this lineage segregation remains elusive. Here, to study symmetry breaking, we use a reduced system in which isolated blastomeres recapitulate the first lineage segregation. We find that in the 8-cell stage embryo, the apical domain recruits a spindle pole to ensure its differential distribution upon division. Daughter cells that inherit the apical domain adopt trophectoderm fate. However, the fate of apolar daughter cells depends on whether their position within the embryo facilitates apical domain formation by Cdh1-independent cell contact. Finally, we develop methods for transplanting apical domains and show that acquisition of this domain is not only required but also sufficient for the first lineage segregation. Thus, we provide mechanistic understanding that reconciles previous models for symmetry breaking in mouse development.
Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
Ekaterina
E
Korotkevich
Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
Ritsuya
R
Niwayama
Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
Aurélien
A
Courtois
Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
Stefanie
S
Friese
Medical Systems Biology, UCC, University Hospital and Medical Faculty Carl Gustav Carus, TU Dresden, 01062 Dresden, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Nicolas
N
Berger
Medical Systems Biology, UCC, University Hospital and Medical Faculty Carl Gustav Carus, TU Dresden, 01062 Dresden, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Frank
F
Buchholz
Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany. Electronic address: hiiragi@embl.de.
Takashi
T
Hiiragi
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002450:Cell Communication; D018797:Cell Cycle Proteins; D019070:Cell Lineage; D016764:Cell Polarity; D004475:Ectoderm / Q000166:cytology; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism; D000091102:YAP-Signaling Proteins
D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse
apico-basal polarity; cell-fate specification; early mammalian development; reduced systems; self-organization; symmetry breaking