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Group Prof. Dr. Schambony

Cell polarity and migration in Xenopus development

 

 

During the development of a complex multicellular organism from a single fertilized oocyte cell types and tissues are specified by differential gene expression patterns. These cells and tissues are organized into the three-dimensional shape of organs and the entire organism by morphogenetic movements. Most morphogenetic movements are coordinated mass cell movements, which require tight regulation of cell polarity, motility and adhesion to maintain tissue integrity during morphogenesis. In addition, cell rearrangements and shape changes go along with modulation of the biomechanics properties of individual cells and tissues and an increased metabolic activity to generate the required energy.

The Wnt family of secreted morphogens activates divergent signaling cascades, which are traditionally divided into one “canonical” Wnt/β-Catenin pathway and multiple “non-canonical” β-Catenin-independent pathways. Wnt signaling cascades, in particular β-catenin-independent Wnt pathways play a major role in the regulation of morphogenetic movements. We are studying different aspects of beta-catenin independent Wnt signaling in morphogenesis in Xenopus laevis.
Xenopus laevis is a non-mammalian vertebrate model organism with extra corporal development. This allows the non-invasive observation of even the earliest steps of development. In addition, the large number of eggs and the easy and efficient transient manipulation of gene expression by microinjection render Xenopus an excellent model for embryology, but also for cell biology and imaging as well as biochemical and biophysical experiments and the recapitulation of human disease (www.xenbase.org).

Signaling by the Receptor Tyrosine Kinase Ror2

The type of co-receptor recruited to the Frizzled receptor complex influences the differential activation of Wnt signaling cascades. LRP 5/6 containing receptor complexes activate the canonical Wnt pathway while RTK-type co-receptors induce activation of non-canonical Wnt pathways. Interestingly, LRP6 and the non-canonical coreceptor Ror2 are regulated by the same kinases and similar to LRP6 Ror2 has also been found associated with different membrane microdomains. As subproject 5 in the newly funded Research Training Group RTG 1962 “Dynamic Interactions at Biological Membranes – from Single Molecules to Tissue” (www.biomembranes.org) we are investigating the mechanisms of Ror2 localization to membrane microdomains and how Ror2 signaling is affected by its subcellular localization.

The Ror2 RTK can act as a bona fide Wnt receptor and it can interact as co-receptor in the Wnt planar cell polarity pathway. Ror2 regulates the expression of paraxial protocadherin during gastrulation and is essential for cell alignment and coordinated polarity and migration of the dorsal mesoderm during convergent extension movements. In collaboration with Marc Gentzel and Andrej Shevchenko (MPI-CBG, Dresden) we have carried out quantitative functional proteomics experiments and observed that Ror2 interacts with multiple cytoskeleton-regulating proteins including Filamin A. Currently, we are investigating how these physical interactions relate to Ror2 signaling and the modulation of cellular biomechanics in collaboration with Ben Fabry’s group (Medizinische Biophysik, FAU; www.biomed.uni-erlangen.de)

 

 

In post-gastrula development, Ror2 is expressed in the Neural Crest, a multipotent progenitor cell population that gives rise to cranial cartilage, melanocytes and to neurons and glia of the peripheral nervous system. In a collaborative project with Prof. Annette Borchers in the Wnt Research Unit 942 “Wnt-signaling in development and tumor progression” www.for942.med.uni-goettingen.de) we are investigating the role of Ror2 in neural crest development and the interaction between Ror2 and PTK7.

 

β-Arrestin and Dishevelled protein complexes as intracellular signaling hubs

The different Wnt pathways are intimately linked by interactions, cross-talk and antagonistic regulation, which led to the emerging opinion that Wnt signaling might be a signaling network rather than a group of distinct pathways. β-Arrestin 2 (Arrb2) is a central protein in different Wnt pathways that interacts with different binding partners and thereby contributes to signal specificity and signal integration. By quantitative functional proteomics (collaboration with Marc Gentzel and Andrej Shevchenko, MPI-CBG Dresden) we have characterized the protein-protein interactions of β-Arrestin / Dishevelled protein complexes and identified new interacting proteins, which we are following up in functional studies in Xenopus embryogenesis.

 

Members

Sabrina Krenn (PhD student)

Verena Rauschenberger (Research Associate)

Lab alumni

Monica De Maria (Research Associate)

Jens Heller (PhD student)

Cornelia Holler (PhD student)

Carolin Schille (PhD student)

Abinash Subudhi (PhD student)

 

Auf diesem Foto sehen Sie die AG PD Dr. Schambony

Group Prof. Dr. Alexandra Schambony (from left to right: Verena Rauschenberger, Monica De Maria, Cornelia Holler, Prof. Dr. Alexandra Schambony, Sabrina Krenn, Moritz Grob, Abinash Subudhi)