Project

Back to overview

In vivo cell biology of organ morphogenesis

English title In vivo cell biology of organ morphogenesis
Applicant Affolter Markus
Number 176400
Funding scheme Project funding (Div. I-III)
Research institution Abteilung Zellbiologie Biozentrum Universität Basel
Institution of higher education University of Basel - BS
Main discipline Embryology, Developmental Biology
Start/End 01.12.2017 - 31.03.2021
Approved amount 1'038'767.00
Show all

Keywords (6)

protein binders; branching morphogenesis; development; angiogenesis; nanobodies; zebrafish

Lay Summary (German)

Lead
Wie sich Organe bilden; eine in vivo Studie mit dem Zebrafisch
Lay summary

Wie sich Organe bilden; eine in vivo Studie mit dem Zebrafisch

Die Bildung von Organen im sich entwickelnden Embryo blieb bis anhin wenig erforscht, da es nicht möglich war, vertiefte Einblicke in das Innenleben des Embryos zu erlangen. Mit Hilfe der Fluoreszenzmikroskope und transgene Fischen, die fluoreszierende Proteine in den Blutgefässen exprimieren, ist es heute möglich, die komplexe Entwicklung der Blutgefässe im Detail und zum ersten Mal im lebendigen Tier zu verfolgen. Unsere Studien zielen darauf ab, ein besseres Verständnis der Blutgefässbildung zu erhalten, und dies auf zellulärer und molekularer Ebene. Unsere Studien sollen dazu beitragen, die Blutgefässbildung besser beeinflussen zu können, um eventuell die vielen Krankheiten, die mit abnormalen Gefässen einhergehen oder durch Letztere verursacht werden, besser behandeln zu können.

Direct link to Lay Summary Last update: 13.10.2017

Responsible applicant and co-applicants

Employees

Publications

Publication
Building the complex architectures of vascular networks: Where to branch, where to connect and where to remodel?
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.
Preface
Affolter Markus (2021), Preface, Elsevier, Academic Press, xi-xiv.
The tight junctions protein Claudin-5 limits endothelial cell motility
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, 1-11.
Sprouting and anastomosis in the Drosophila trachea and the vertebrate vasculature: Similarities and differences in cell behaviour
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.
Junction-based lamellipodia drive endothelial cell rearrangements in vivo via a VE-cadherin-F-actin based oscillatory cell-cell interaction
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.
Wnt/β-catenin signaling regulates VE-cadherin-mediated anastomosis of brain capillaries by counteracting S1pr1 signaling
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.
Endothelial cell rearrangements during vascular patterning require PI3-kinase-mediated inhibition of actomyosin contractility
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.

Collaboration

Group / person Country
Types of collaboration
Andreas Plückthun Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Anne Spang Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Rob Parton Australia (Oceania)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Associated projects

Number Title Start Funding scheme
156838 In vivo cell biology of organ morphogenesis 01.12.2014 Project funding (Div. I-III)
200701 Angiogenesis in zebrafish: how are vascular networks formed? 01.04.2021 Project funding (Div. I-III)

Abstract

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.
-