Laboratory of the Structure and Function of Living Matter

Research interests

There is evidence that Notch can signal independently of this transcriptional activity. This Su(H) independent activity targets Armadillo, that is the Drosophila homologue of ß-catenin, and the effector of Wnt signalling. A function for Notch in the modulation of this signalling pathway has been analyzed over the years in AMA’s lab. These analyses have provided a basis to interpret reports of interactions that exist in the literature and a framework to probe into the mechanism. Using Drosophila wing imaginal discs as model system, we have shown that the activity of Notch that modulates the activity of ß-catenin is tightly associated with the ligand independent traffic of Notch. Furthermore, we have also shown that Wnt is able to regulate the activity of Notch by promoting its ligand-independent traffic. These results have let us to propose that Wnt and Notch from a single functional device that we call Wntch.

We are currently using mouse embryonic stem cells (mES) to asses some of these concepts. mES cells are cultured pluripotent cell populations derived from the inner cell mass of preimplatation epiblasts. These cells can self-renew in culture in an undifferentiated state, but also they maintain the capacity to generate any cell type in the body. This is consistent with the observation that there is a high degree of heterogeneity in mES cells in the same culture, with cells that show high levels of the core pluripotency genes, among others with lower levels that are more prone to differentiation. Therefore it is important to maintain this heterogeneity, but also in a balanced manner. Wnt can influence the cell state (and probably the heterogeneity) in the presence of other pluripotency factors by maintaining a balance between self-renew and differentiation. According to this model, Wnt would be responsible for pushing the cells into a self-renewal state. In order to keep the balance, there must be a mechanism that regulates Wnt activity. We think that Wntch might be modulating the balance between self-renew and differentiation in mES cells.

Recent publications

1. Munoz-Descalzo, S., Sanders, P. G., Montagne, C., Johnson, R. I., Balayo, T. and Arias, A. M. Wingless modulates the ligand independent traffic of Notch through Dishevelled. Fly (Austin) 4

2. Sanders, P. G., Munoz-Descalzo, S., Balayo, T., Wirtz-Peitz, F., Hayward, P. and Arias, A. M. (2009). Ligand-independent traffic of Notch buffers activated Armadillo in Drosophila. PLoS Biol 7, e1000169

3. Kalmar, T., Lim, C., Hayward, P., Munoz-Descalzo, S., Nichols, J., Garcia-Ojalvo, J. and Martinez Arias, A. (2009). Regulated fluctuations in nanog expression mediate cell fate decisions in embryonic stem cells. PLoS Biol 7, e1000149

Page updated 20 October 2010