We have postdoctoral positions and fully funded PhD student positions available!
Welcome to our group webpage! We are a joint research group between the Max Planck Institute for the Physics of Complex Systems (MPI-PKS) and the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), based at the Center for Systems Biology Dresden (CSBD), established in 2021.
We are theorists, but we closely collaborate with experimentalists, at MPI-CBG and beyond, on problems in theoretical biophysics, applied mathematics, and soft matter physics. Read more about our research.
Looking for a PhD or postdoc position? Read more about how to join us.
Julien Delpierre, José I. Valenzuela, Matthew J. Bovyn, Nuno Pimpao Martins, Lenka Belicova, Urska Repnik, Maarten P. Bebelman, Sarah Seifert, Pierre A. Haas, L. Yannis Kalaidzidis, and Marino Zerial#, bioRxiv (2024)
Hepatocytes have a unique multiaxial polarity with several apical and basal surfaces. The prevailing model for the emergence of this multipolarity and the coordination of lumen formation between adjacent hepatocytes is based on asymmetric cell division. Here, investigating polarity generation in liver cell progenitors, the hepatoblasts, during liver development in vivo and in vitro, we found that this model cannot explain the observed dynamics of apical lumen formation in the embryonic liver. Instead, we identified a new mechanism of multi-axial polarization: We found that polarization can be initiated in a cell-autonomous manner by re-positioning apical recycling endosomes (AREs) to the cell cortex via fibronectin sensing through Integrin αV. Using live cell imaging we showed that this process repeats, leading to multiaxial polarity independently of cell division. We found that the establishment of oriented trafficking leads to the secretion of the metalloprotease MMP13, allowing neighboring hepatoblasts to synchronize their polarization by sensing extracellular matrix (ECM) distribution and enabling lumen opening. Finally, active remodeling of ECM in the proximity of nascent apical surfaces closes a positive feedback loop of polarization, whereas disruption of this loop by either blocking MMP13 or downregulating Integrin αV prevents the formation of the bile canaliculi network. Integration of this feedback loop into a simple mathematical model reproduces the observed dynamics of bile canaliculi network formation during liver development quantitatively. Our combined findings thus suggest a new mechanism of polarization coupling to self-organization at the tissue scale.