Developmental clock and mechanism of de novo polarization of the mouse embryo.
American Association for the Advancement of Science
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Zhu, M., Cornwall-Scoones, J., Wang, P., Handford, C., Na, J., Thomson, M., & Zernicka-Goetz, M. (2020). Developmental clock and mechanism of de novo polarization of the mouse embryo.. Science, 370 (6522)https://doi.org/10.1126/science.abd2703
Embryo polarization is critical for mouse development; however, neither the regulatory clock nor the molecular trigger that it activates is known. Here, we show that the embryo polarization clock reflects the onset of zygotic genome activation, and we identify three factors required to trigger polarization. Advancing the timing of transcription factor AP-2 gamma (Tfap2c) and TEA domain transcription factor 4 (Tead4) expression in the presence of activated Ras homolog family member A (RhoA) induces precocious polarization as well as subsequent cell fate specification and morphogenesis. Tfap2c and Tead4 induce expression of actin regulators that control the recruitment of apical proteins on the membrane, whereas RhoA regulates their lateral mobility, allowing the emergence of the apical domain. Thus, Tfap2c, Tead4, and RhoA are regulators for the onset of polarization and cell fate segregation in the mouse.
Actins, Animals, Biological Clocks, Blastocyst, Cell Differentiation, Cell Polarity, Cytoskeletal Proteins, DNA-Binding Proteins, Embryonic Development, Female, Gene Knockdown Techniques, Mice, Mice, Inbred C57BL, Muscle Proteins, RNA Interference, Transcription Factor AP-2, Transcription Factors, rhoA GTP-Binding Protein
Wellcome Trust (098287/Z/12/Z)
ECH2020 EUROPEAN RESEARCH COUNCIL (ERC) (669198)
External DOI: https://doi.org/10.1126/science.abd2703
This record's URL: https://www.repository.cam.ac.uk/handle/1810/318318
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