Carl-Philipp Heisenberg

Genetic and cellular control of gastrulation movements in zebrafish

Previous and current research

We are interested in the cellular mechanisms that underlie morphogenic movements during zebrafish gastrulation. There are three main types of cellular rearrangements during zebrafish gastrulation: involution of mesendodermal cells, followed by dorsal convergence, the accumulation of cells at the dorsal side of the gastrula, and convergent extension, the spreading of cells along the future anterior-posterior axis of the embryo. We are investigating the genetic and cellular basis of tissue morphogenesis during gastrulation by analysing existing zebrafish mutants showing defective gastrulation movements such as silberblick (slb), trilobite and knypek, and by identifying further mutants with related phenotypes.

We have recently shown that the slb locus encodes wnt11 and that the Wnt11 downstream signalling pathway shares components with Wnt signalling involved in the establishment of planar polarity in Drosophila. We also demonstrated that Wnt11 function is needed within paraxial tissues of the gastrula to regulate medial-lateral cell intercalation leading to convergent extension of both paraxial and axial tissues.

We have started to analyse the pattern of cell movement during convergent extension in wild type and slb embryos by using timelapse microscopy followed by single cell tracking. We have also set up a mutagenesis screen aiming to identify mutants that can enhance or suppress the slb phenotype (enhancer and suppressor screen). This should lead to the identification of further components of the Wnt11 signalling cascade.

The broad context of this work aims to evaluate the contribution of single genes to cell movements and cell shape changes and to establish how cellular rearrangements contribute to tissue morphogenesis during zebrafish gastrulation.

3-dimensional reconstruction of single ectodermal progenitor cells at the onset of zebrafish gastrulation - the picture was taken with a 2-photon laser scanning microscope and the cells were rendered using Volocity imaging software (Improvision)

Future prospects and goals

• Identification of loci interacting (enhancing or suppressing) with Slb/Wnt11 during convergent extension by conducting a mutagenesis screen.
• Analysis of cell movements and cell shape changes during convergent extension in wild type and mutant (slb, trilobite, knypek) embryos using time lapse microscopy and single cell tracking.
• Establishment and analysis of transgenic zebrafish lines expressing GFP under the control of wnt11 promoter elements to allow live imaging of wnt11 expression in single cells during gastrulation.
  
  

About

1996: PhD in Biology, University of Tübingen 1996-2000: Postdoctoral fellow at King´s College London/ University College London since 2000: Group Leader at the Max Planck Institute of Molecular Cell Biology and Genetics

Selected publications

Ulrich F, Krieg M, Schotz EM, Link V, Castanon I, Schnabel V, Taubenberger A, Mueller D, Puech PH, Heisenberg CP. (2005): Wnt11 functions in gastrulation by controlling cell cohesion through Rab5c and E-cadherin. Dev Cell. 2005 Oct;9(4):555-64.

Puech PH, Taubenberger A, Ulrich F, Krieg M, Muller DJ, Heisenberg CP. (2005): Measuring cell adhesion forces of primary gastrulating cells from zebrafish using atomic force microscopy. J Cell Sci. 2005 Sep 15;118(Pt 18):4199-206.

Montero JA, Carvalho L, Wilsch-Brauninger M, Kilian B, Mustafa C, Heisenberg CP. (2005): Shield formation at the onset of zebrafish gastrulation. Development. 2005 Mar;132(6):1187-98. Epub 2005 Feb 9.

Ulrich, F., Concha, M. L, Heid, P. J., Voss, E., Witzel, S., Roehl, H., Tada, M., Wilson, S. W., Adams, R. J., Soll, D. R. and Heisenberg, C. P. (2003): Slb/Wnt11 controls hypoblast cell migration and morphogenesis at the onset of zebrafish gastrulation. Development, 130(22): 5375-84

Montero, J. A., Kilian, B., Chan, J., Bayliss, P. E. and Heisenberg, C. P. (2003): Phosphoinositide 3-kinase is required for process outgrowth and cell polarization of gastrulating mesendodermal cells. Curr Biol., 13(15): 1279-89

Heisenberg, C. P., Houart, C., Take-Uchi, M., Rauch, G. J., Young, N., Coutinho, P., Masai, I., Caneparo, L., Concha, M. L., Geisler, R., Dale, T. C., Wilson, S. W. and Stemple, D. L. (2001): A mutation in the Gsk3-binding domain of zebrafish Masterblind/Axin1 leads to a fate transformation of telencephalon and eyes to diencephalon. Genes Dev., 15(11): 1427-34

Heisenberg, C. P., Tada, M., Rauch, G. J., Saude, L., Concha, M. L., Geisler, R., Stemple, D. L., Smith, J. C. and Wilson, S. W. (2000): Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation. Nature, 405(6782): 76-81

Heisenberg, C. P. and Nusslein-Volhard, C. (1997): The function of silberblick in the positioning of the eye anlage in the zebrafish embryo. Dev Biol., 184(1): 85-94

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