title: Initiation of Hippo signaling is linked to polarity rather than to cell position in the pre-implantation mouse embryo.
abstract: In the mouse embryo, asymmetric divisions during the 8-16 cell division generate two cell types, polar and apolar cells, that are allocated to outer and inner positions, respectively. This outer/inner configuration is the first sign of the formation of the first two cell lineages: trophectoderm (TE) and inner cell mass (ICM). Outer polar cells become TE and give rise to the placenta, whereas inner apolar cells become ICM and give rise to the embryo proper and yolk sac. Here, we analyze the frequency of asymmetric divisions during the 8-16 cell division and assess the relationships between cell polarity, cell and nuclear position, and Hippo signaling activation, the pathway that initiates lineage-specific gene expression in 16-cell embryos. Although the frequency of asymmetric divisions varied in each embryo, we found that more than six blastomeres divided asymmetrically in most embryos. Interestingly, many apolar cells in 16-cell embryos were located at outer positions, whereas only one or two apolar cells were located at inner positions. Live imaging analysis showed that outer apolar cells were eventually internalized by surrounding polar cells. Using isolated 8-cell blastomeres, we carefully analyzed the internalization process of apolar cells and found indications of higher cortical tension in apolar cells than in polar cells. Last, we found that apolar cells activate Hippo signaling prior to taking inner positions. Our results suggest that polar and apolar cells have intrinsic differences that establish outer/inner configuration and differentially regulate Hippo signaling to activate lineage-specific gene expression programs.
authors.affiliation: Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West, Montreal, QC H3A1A3, Canada Department of Human Genetics, McGill University, 1160 Pine Avenue West, Montreal, QC H3A1A3, Canada.
authors.forename: Shihadeh
authors.initials: S
authors.lastname: Anani
authors.affiliation: Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West, Montreal, QC H3A1A3, Canada.
authors.forename: Shivani
authors.initials: S
authors.lastname: Bhat
authors.affiliation: Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West, Montreal, QC H3A1A3, Canada.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Honma-Yamanaka
authors.affiliation: Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West, Montreal, QC H3A1A3, Canada.
authors.forename: Dayana
authors.initials: D
authors.lastname: Krawchuk
authors.affiliation: Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West, Montreal, QC H3A1A3, Canada Department of Human Genetics, McGill University, 1160 Pine Avenue West, Montreal, QC H3A1A3, Canada yojiro.yamanaka@mcgill.ca.
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Yamanaka
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D060049:Asymmetric Cell Division; D001755:Blastocyst / Q000166:cytology* / Q000378:metabolism*; D001757:Blastomeres / Q000166:cytology / Q000378:metabolism; D002450:Cell Communication; D002452:Cell Count; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism; D016764:Cell Polarity; D000090683:Hippo Signaling Pathway; D051379:Mice; D018994:Myosin Light Chains / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D018994:Myosin Light Chains; D010750:Phosphoproteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D017346:Protein Serine-Threonine Kinases
keywords: 16-cell stage; Asymmetric division; Cell sorting; Inner cell mass (ICM); Live imaging; Mouse; Trophectoderm (TE); YAP (Yes-associated protein)