AG Dr. Jubin Kashef (Young Investigator Group)

Mechanism of Cadherin dependent cell migration


Cadherins represent a multigene family of cell surface glycoproteins that mediate Ca2+-dependent homophilic cell-cell adhesion. Their function is not only limited to mechanical adhesion between cells, but they play an important role in cell-cell signalling as well. Initially, cadherins were identified in epithelia required for cell polarity and for establishing tissue integrity. In the embryo, a switch in cadherin subtype expression promotes tissue separation while in tumors the loss of E-cadherin and up-regulation of N-cadherin or Cadherin-11 often correlates with high invasiveness.

We are investigating the function of Cadherin-11 in the Xenopus laevis model system, where Cadherin-11 is mainly expressed in the cranial neural crest (CNC). The cranial neural crest is a multipotent and highly migratory cell population that shapes the vertebrate face contributing to the craniofacial bones, cartilage, and ganglia. Although it is extremely motile, the CNC continually expresses the cell-cell adhesion molecule Cadherin-11. In adult tissues, up-regulation of Cadherin-11 coincides with tumor progression and cartilage invasion by synoviocytes in inflammatory arthritis. These observations point to a migration-stimulating property of Cadherin-11 distinct from its cell-adhesive function. Thus, the question arises how Cadherin-11, as an adhesion molecule, is stimulating cell migration. Our aim is to characterize the mechanism how cadherins promote cell migration which will have a strong implications on understanding cell invasion in a variety of different diseases.


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Movie 3
Analysis of CNC migration in vitro. Control explants of membrane GFP and histon RFP injected embryos were cultured in vitro on fibronectin for several hours. Note that control CNC show extensive protrusive activity and form filopodia and lamellipodia.
Note that Xcadherin-11 depleted CNC are not able to form filopodia and lamellipodia. They have a round cell shape and only show membrane blebbing.
Protrusion activity of wildtype CNC in vivo. Transplants of membrane GFP labelled CNC were examined at tadpole stage. Extensive filopodia formation could be observed in several cells.


°  Establishing time-lapse X-ray phase-contrast microtomography for in vivo imaging of morphogenesis in developmental biology
Moosmann J., Ershov A., Altapova V., Baumbach T., Prasad M.S., LaBonne C., Xiao X., Kashef J.*, Hofmann R.* (2014)
Nature Protocols, 9(2):294-304. doi: 10.1038/nprot.2014
°  Cadherin-11 mediates contact inhibition of locomotion during Xenopus neural crest cell migration
Becker, S.F., Mayor, R, Kashef, J. (2013)
PLoS One, 8(12):e85717. doi: 10.1371/journal.pone.0085717.
°  Par3 controls neural crest migration by promoting microtubule catastrophe during contact inhibition of locomotion
Moore,R., Theveneau, E., Pozzi,S., Alexandre,P., Richardson,J., Merks, A., Parsons, M., Kashef, J., Linker,C. and Mayor, R. (2013)
Development, 140(23), 4763-75
°  Loss of Xenopus cadherin-11 leads to increased Wnt/β-catenin signaling and up-regulation of target genes c-myc and cyclin D1 in neural crest
Koehler A., Schlupf J., Schneider M., Kraft B., Winter C., Kashef J. (2013)
Developmental Biology, 383, 132-145
°  X-ray phase-contrast in vivo microtomography probes new aspects of Xenopus gastrulation
Moosmann J., Ershov A., Altapova V., Baumbach T., Prasad M.S., LaBonne C., Xiao X., Kashef J.*, Hofmann R.* (2013)
Nature 497, 374–377 (16 May 2013) | doi:10.1038/nature12116   
Nature Article
Nature methods - research highlights "Embryos under the X-ray"
Pressemitteilung D
Pressemitteilung E
°  Diffusion- and convection-based activation of Wnt/β-catenin signaling in a gradient generating microfluidic chip
Kim, C., Kreppenhofer, K., Kashef, J., Gradl, D., Herrmann, D., Schneider, M., Ahrens, R., Guber, A. and Wedlich, D. (2012)
Lab Chip. 2012 Dec 21;12(24):5186-94. doi: 10.1039/c2lc40172j.
°  Expression of the tetraspanin family members Tspan3, Tspan4, Tspan5 and Tspan7 during Xenopus laevis embryonic development
Kashef, J.*, Diana, T., Oelgeschläger, M., Nazarenko, I.* (2012)
Gene Expression Patterns (2012) Science direct
°  Giving the right tug for migration: Cadherins in tissue movements
Becker, SF., Langhe, R., Huang, C., Wedlich, D. and Kashef, J. (2012)
Arch Biochem Biophys. 2012 Aug 1;524(1):30-42. doi: 10.1016/ Epub 2012 Mar 3. Review
°  Cadherin-11 regulates protrusive activity in Xenpous cranial neural crest cells upstream of Trio and the small GTPases
Kashef, J., Köhler, A., Kuriyama, S., Alfandari, D., Mayor, R. and Wedlich, D. (2009) Genes & Development 2009, 23: 1393-1398
°  Fluchthelfer statt Ordnungshüter
°  Cadherin-11 regulates protrusive activity in Xenopus cranial neural crest cells upstream of Trio and the small GTPases.
F1000 Biology
°  Die Routenplaner der Neuralleistenzellen
Kashef, J., Köhler, A., Wedlich, D. (2007) Biospektrum 3, 242- 245.
°  Xenopus Teashirt1 regulates posterior identity in brain and cranial neural crest
Koebernick, K., Kashef, J., Pieler, T. and Wedlich D. (2006)
Dev Biol. 298, 312-326
     *) corresponding authors


 • Roberto Mayor, University College London, United Kingdom
 • Dominique Alfandari, University of Massechusetts, USA
 • Martin Bastmeyer, KIT, Germany
 • Clemens Franz, KIT, Germany
 • Vita Bryja, Masaryk University, Brno, Czech Republic
 • Andre Menke, Justus-Liebig-Universität Gießen, Germany
 • Annette Borchers, University of Göttingen, Germany
 • Ralf Hofman, KIT, Germany
 • Irina Nazarenko, University of Freiburg, Germany


Claudia Winter (technician)

Formerly staff:
- Chaolie Huang (PhD student)
- Sarah Eria Becker (PhD student)
- Laura Krämer (Apprentice)
- Velia Schall (Bachelor student)
- Thea Vogel (Bachelor student)
- Rahul Langhe (PhD student)
- Anne Merks (Graduant)