The role of mitotic asymmetries for Wnt and Bmp signaling

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Wnt signaling is active in embryonic stem cells and important for anterior-posterior (head-tail) axis establishment during embryogenesis. Bmp signaling controls the dorso-ventral (back-belly) axis and together Wnt and Bmp create a Cartesian coordinate system in the embryo. Intercommunication has been shown at the level of the Bmp transcription factor Smad1, whose degradation is prevented by Wnt signals. Importantly, Smad1 and many other proteins tagged for degradation by phosphorylation unequally accumulate near the cell nucleus of dividing embryonic and somatic cells. Thus, one of the daughter cell inherits more of the relevant proteins, raising questions about the regulation of this mechanism and its function for cell divisions and embryonic development. In preliminary cell line experiments we found this process of asymmetric sorting significantly increased by Wnt treatment. Importantly, this caused asymmetric accumulation of activated signaling components in the nucleus of the corresponding cell as well. In this project, I will first investigate the nature of the influence of Wnt signals on cellular asymmetries. As a second part, I will analyze if these asymmetries reflect differences in signaling activity of two daughter cells by using different approaches. It would be of great importance to reveal if Wnt and Bmp signaling are asymmetric as well, implying different fates for the daughter cells. Finally, these analyses will be extended to embryos to uncover if this is a general polarity phenomenon of dividing cells and to connect the features with overall regulation of axis development by Wnt and Bmp. In sum, this project will help to explain how general binary decisions made during cell division are related to embryonic axis development in complex embryos.