protein binders; branching morphogenesis; development; angiogenesis; nanobodies; zebrafish
Yin Jianmin, Heutschi Daniel, Belting Heinz-Georg, Affolter Markus (2021), Building the complex architectures of vascular networks: Where to branch, where to connect and where to remodel?, Elsevier, Academic Press, 281-297.
Affolter Markus (2021), Preface, Elsevier, Academic Press, xi-xiv.
Yang Zhenguo, Wu Shuilong, Fontana Federica, Li Yanyu, Xiao Wei, Gao Zhangdai, Stephan Alice, Affolter Markus, Belting Heinz-Georg, Abdelilah-Seyfried Salim, Zhang Jingjing (2020), The tight junctions protein Claudin-5 limits endothelial cell motility, in Journal of Cell Science
Kotini Maria Paraskevi, Mäe Maarja Andaloussi, Belting Heinz-Georg, Betsholtz Christer, Affolter Markus (2019), Sprouting and anastomosis in the Drosophila trachea and the vertebrate vasculature: Similarities and differences in cell behaviour, in Vascular Pharmacology
, 112, 8-16.
Paatero Ilkka, Sauteur Loïc, Lee Minkyoung, Lagendijk Anne K., Heutschi Daniel, Wiesner Cora, Guzmán Camilo, Bieli Dimitri, Hogan Benjamin M., Affolter Markus, Belting Heinz-Georg (2018), Junction-based lamellipodia drive endothelial cell rearrangements in vivo via a VE-cadherin-F-actin based oscillatory cell-cell interaction, in Nature Communications
, 9(1), 3545-3545.
Hübner Kathleen, Cabochette Pauline, Diéguez-Hurtado Rodrigo, Wiesner Cora, Wakayama Yuki, Grassme Kathrin S., Hubert Marvin, Guenther Stefan, Belting Heinz-Georg, Affolter Markus, Adams Ralf H., Vanhollebeke Benoit, Herzog Wiebke (2018), Wnt/β-catenin signaling regulates VE-cadherin-mediated anastomosis of brain capillaries by counteracting S1pr1 signaling, in Nature Communications
, 9(1), 4860-4860.
Angulo-Urarte Ana, Casado Pedro, Castillo Sandra D., Kobialka Piotr, Kotini Maria Paraskevi, Figueiredo Ana M., Castel Pau, Rajeeve Vinothini, Milà-Guasch Maria, Millan Jaime, Wiesner Cora, Serra Helena, Muixi Laia, Casanovas Oriol, Viñals Francesc, Affolter Markus, Gerhardt Holger, Huveneers Stephan, Belting Heinz-Georg, Cutillas Pedro R., Graupera Mariona (2018), Endothelial cell rearrangements during vascular patterning require PI3-kinase-mediated inhibition of actomyosin contractility, in Nature Communications
, 9(1), 4826-4826.
In vivo cell biology of organ morphogenesisSummary of the research planOrgans and tissue acquire particular three-dimensional shapes during development, which are intimately linked to particular functions an organ has to fulfil. Organ shape is to a large extent determined by cell behaviour and cell behaviour is to a large extent regulated by cell-cell interaction and cell-matrix interaction, as well as by cell-cell signalling.A major interest of my laboratory over the last few years has been to determine how branching morphogenesis restructures epithelial or endothelial structures such as the insect tracheal or the vertebrate vasculature. We have used high resolution live imaging with different marker proteins to analyse cell behaviour in vivo during the branching process. We are now increasing our efforts to better understand the molecular control of the relevant cell behaviours. With the help of the recently introduced genome editing tool Crispr/Cas, the task to mutate candidate genes has become straightforward, and we have already generate several mutants and characterized their role in angiogenesis. Since many genes/proteins are actively rather broadly and are required for basic cell functions such as cellular trafficking, cell division, etc., we have started to develop protein-manipulation tools which eventually should allow us to manipulate proteins in a cell- and time-induced manner. These tools are based on protein binders and we have pioneered the use of the later in multicellular systems some time ago. We are developing such protein-binder tools for proteins of interest in order to use them for protein trapping, degradation, miss-localization, ect. These studies should allow a novel view on the role of many proteins in angiogenesis, and pave the way to a molecular understanding of the fascinating process of branching morphogenesis.In the next granting period, we would like to address the following questions:1)How are cell rearrangement controlled and coordinated during the different steps of angiogenesis?2)How is the lumen formed during sprouting and anastomosis3)How are cell rearrangements and lumen formation controlled at the molecular level?In order to answer these questions, we will take the following experimental strategies:1)We will analyse the role of several proteins involved in the regulation of Ve-cadherin in cell rearrangements.2)We will analyse the role of trafficking in cell rearrangement and lumen formation.3)We will develop novel protein binder tools to manipulate proteins possibly involved in the above processes in a cell- and time-specific manner.4)We will try to establish CLEM in order to look at high resolution into endothelial cell during the branching process.