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9. Tead4and Tfap2cgenerate bipotency and a bistable switch in totipotent embryos to promote robust lineage diversification

Author

Zhu, Meng, Meglicki, Maciej, Lamba, Adiyant, Wang, Peizhe, Royer, Christophe, Turner, Karen, Jauhar, Muhammad Abdullah, Jones, Celine, Child, Tim, Coward, Kevin, Na, Jie, and Zernicka-Goetz, Magdalena

Abstract

The mouse and human embryo gradually loses totipotency before diversifying into the inner cell mass (ICM, future organism) and trophectoderm (TE, future placenta). The transcription factors TFAP2C and TEAD4 with activated RHOA accelerate embryo polarization. Here we show that these factors also accelerate the loss of totipotency. TFAP2C and TEAD4 paradoxically promote and inhibit Hippo signaling before lineage diversification: they drive expression of multiple Hippo regulators while also promoting apical domain formation, which inactivates Hippo. Each factor activates TE specifiers in bipotent cells, while TFAP2C also activates specifiers of the ICM fate. Asymmetric segregation of the apical domain reconciles the opposing regulation of Hippo signaling into Hippo OFF and the TE fate, or Hippo ON and the ICM fate. We propose that the bistable switch established by TFAP2C and TEAD4 is exploited to trigger robust lineage diversification in the developing embryo.

Published
2024
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14. ASPP2/PP1 complexes maintain the integrity of pseudostratified epithelia undergoing remodelling during morphogenesis

Author

Royer, Christophe, primary, Sandham, Elizabeth, additional, Slee, Elizabeth, additional, Godwin, Jonathan, additional, Veits, Nisha, additional, Hathrell, Holly, additional, zhou, Felix, additional, Leonavicius, karolis, additional, Garratt, Jemma, additional, Narendra, Tanaya, additional, Vincent, Anna, additional, Jones, Celine, additional, Child, Tim, additional, Coward, Kevin, additional, Graham, Chris, additional, Lu, Xin, additional, and Srini, Shankar, additional

Published
2020
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15. YAP and CDX2 distribution from Spatial protein analysis in developing tissues: a sampling-based image processing approach

Author

Leonavicius, Karolis, Royer, Christophe, Miranda, Antonio M. A., Tyser, Richard C. V., Kip, Annemarie, and Srinivas, Shankar

Subjects
embryonic structures, digestive system diseases
Abstract

Comparison of manual cell outlining and SilentMark performance. Distributions of measured values of Yap and Cdx2 nuclear/cytoplasmic ratios.

Published
2020
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22. ASPP2 controls epithelial plasticity and inhibits metastasis through β-catenin-dependent regulation of ZEB1

Author

Wang, Yihua, primary, Bu, Fangfang, additional, Royer, Christophe, additional, Serres, Sébastien, additional, Larkin, James R., additional, Soto, Manuel Sarmiento, additional, Sibson, Nicola R., additional, Salter, Victoria, additional, Fritzsche, Florian, additional, Turnquist, Casmir, additional, Koch, Sofia, additional, Zak, Jaroslav, additional, Zhong, Shan, additional, Wu, Guobin, additional, Liang, Anmin, additional, Olofsen, Patricia A., additional, Moch, Holger, additional, Hancock, David C., additional, Downward, Julian, additional, Goldin, Robert D., additional, Zhao, Jian, additional, Tong, Xin, additional, Guo, Yajun, additional, and Lu, Xin, additional

Published
2014
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24. Thermodynamic Limits for Hamiltonians Defined as Pseudodifferential Operators.

Author

Nourrigat, Jean and Royer, Christophe

Subjects
*HAMILTONIAN operator, *DIFFERENTIAL operators, *PARTIAL differential equations, *DIFFERENTIAL equations, *ASYMPTOTIC expansions, *CALCULUS
Abstract

If P(h) is a h-pseudodifferential operator in Rn associated to an holomorphic semi-bounded symbol in some neighborhood of the real phase space, with bounded derivatives, we describe the symbol of e-tP(h), by inequalities where the constants depend on the bounds for the derivatives of the symbol of P(h), but not on the dimension n. Some applications to thermodynamic limits (free energy) are given. [ABSTRACT FROM AUTHOR]

Published
2004

25. Mechanical and geometric cues guiding early mammalian tissue development

Author

Leonavicius, Karolis, Srinivas, Shankar, Royer, Christophe, and Vollrath, Fritz

Subjects
571.8
Abstract

Mammalian development is one of the most complex biological processes, that is responsible for converting a single cell into a whole organism. Al- though, mechanical forces are expected to play profound roles during de- velopment, proving the role of mechanical and geometric cues has been difficult due to the lack of suitable experimental techniques. The thesis investigates the hypothesis, that mechanical and geometric cues are driv- ing the first two cell fate decision events. In order to test them and create a robust experimental framework, the first three chapters are dedicated to developing methodology based on three dimensional patterned hydrogels. The hydrogels were mechanically and biochemically characterised in high detail and then used as three dimensional moulds to shape developing tis- sues. This technique also made it possible to calculate mechanical forces, which could be estimated from hydrogel deformation and known elastic properties. Finally, to characterise the biological outcomes of mechani- cal tissue deformation a heuristic confocal image analysis technique has been developed and used to investigate developing mammalian tissues. Using the techniques it was possible to demonstrate, that the first cell fate decision is controlled by embryo geometry and the molecular mecha- nism involved a complex combination of Hippo pathway signalling and a sequence of cell polarisation. Similarly, the second cell fate decision was also found to be driven by tissue geometry and Hippo pathway signalling, although the precise biochemical pathway was less clear.

Published
2016

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