TEAD4 Regulates apical domain homeostasis and cell-positioning to maintain the trophectoderm lineage during mouse blastocyst development
- 1Department of Molecular Biology and Genetics (Faculty of Science), University of South Bohemia in Ceske Budejovice 1 , Ceske Budejovice, South Bohemian Region, Czech Republic
- 2Institute of Animal Physiology and Genetics CAS 2 , Liběchov, Central Bohemian Region, Czech Republic
- 3Centre de Recherche du Centre Hospitalier de l'Universite de Montreal 3 , Montreal, Quebec, Canada
Abstract
In mammalian preimplantation embryos, distinct cell lineages occupy defined spatial niches. The outer trophectoderm (TE) forms an epithelial monolayer surrounding the inner cell mass (ICM) and blastocyst cavity. In mice, the Tead4 gene encodes a polarity-dependent transcription factor required for TE specification. Here, we demonstrate that Tead4 also preserves TE integrity during blastocyst maturation. Clonal siRNA-mediated Tead4 knockdown (KD) disrupts outer cell apical domain morphology, causing abnormal allocation of these clones to an enlarged ICM, despite minimal impact on established polarity. Fixed sample and live embryo light-sheet microscopy imaging reveal that TEAD4-deficient outer cells atypically migrate into the blastocyst ICM, sometimes via apical domain abscission, or are repositioned post-division, linking disrupted apical domain morphology to altered spatial positioning and fate. Transcriptomic analysis indicates that TEAD4 regulates genes involved in cytoskeletal organization, particularly those related to actin and cell adhesion, which we propose are critical for maintaining outer cell TE positioning. Combined KD of Tead4 and two of its targets, the atypical GTPases Rnd1 and Rnd3, partially rescues misallocation but does not prevent apical morphological abnormalities. These findings indicate TEAD4 and its downstream regulatory network actively contribute to blastocyst TE maintenance, beyond initial specification, up until the peri-implantation stage, ensuring proper lineage segregation.
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BibTeX
@article{collier2026tead4,
title = {{TEAD4 Regulates apical domain homeostasis and cell-positioning to maintain the trophectoderm lineage during mouse blastocyst development}},
author = {Rebecca Collier and Martina Bohuslavová and Michaela Vaškovičová and Aleksandar I. Mihajlović and Andrea Hauserová and Valeriya Zabelina and Monika Fluks and Lenka Gahurová and Dávid Drutovič and Alexander W. Bruce},
journal = {Open Biology},
year = {2026},
month = oct,
doi = {10.1098/rsob.250441},
url = {https://royalsocietypublishing.org/rsob/article/16/10/250441/483543/TEAD4-Regulates-apical-domain-homeostasis-and-cell},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - TEAD4 Regulates apical domain homeostasis and cell-positioning to maintain the trophectoderm lineage during mouse blastocyst development
AU - Rebecca Collier
AU - Martina Bohuslavová
AU - Michaela Vaškovičová
AU - Aleksandar I. Mihajlović
AU - Andrea Hauserová
AU - Valeriya Zabelina
AU - Monika Fluks
AU - Lenka Gahurová
AU - Dávid Drutovič
AU - Alexander W. Bruce
PY - 2026
DA - 2026/10/07
JO - Open Biology
DO - 10.1098/rsob.250441
UR - https://royalsocietypublishing.org/rsob/article/16/10/250441/483543/TEAD4-Regulates-apical-domain-homeostasis-and-cell
AB - In mammalian preimplantation embryos, distinct cell lineages occupy defined spatial niches. The outer trophectoderm (TE) forms an epithelial monolayer surrounding the inner cell mass (ICM) and blastocyst cavity. In mice, the Tead4 gene encodes a polarity-dependent transcription factor required for TE specification. Here, we demonstrate that Tead4 also preserves TE integrity during blastocyst maturation. Clonal siRNA-mediated Tead4 knockdown (KD) disrupts outer cell apical domain morphology, causing abnormal allocation of these clones to an enlarged ICM, despite minimal impact on established polarity. Fixed sample and live embryo light-sheet microscopy imaging reveal that TEAD4-deficient outer cells atypically migrate into the blastocyst ICM, sometimes via apical domain abscission, or are repositioned post-division, linking disrupted apical domain morphology to altered spatial positioning and fate. Transcriptomic analysis indicates that TEAD4 regulates genes involved in cytoskeletal organization, particularly those related to actin and cell adhesion, which we propose are critical for maintaining outer cell TE positioning. Combined KD of Tead4 and two of its targets, the atypical GTPases Rnd1 and Rnd3, partially rescues misallocation but does not prevent apical morphological abnormalities. These findings indicate TEAD4 and its downstream regulatory network actively contribute to blastocyst TE maintenance, beyond initial specification, up until the peri-implantation stage, ensuring proper lineage segregation.
SN - 2046-2441
ER -