BIOTEC - Biotechnology Center TU Dresden

Our group focuses on two aspects of developmental biology:

(1) The extracellular signaling mechanisms that regulate zebrafish fin and heart regeneration
(2) Downstream mediators and modulators of Wnt/beta-catenin signaling

All animals have evolved strategies to deal with damage due to injury or disease, but the ability to regenerate lost or damaged organs and appendages varies greatly in different species. Unfortunately, humans and other mammals are quite poor at regenerating, while other vertebrates, like salamanders and fish, can efficiently re-grow lost limbs/fins and regenerate many internal organs and even the central nervous system. Currently it is a mystery why mammals can’t do what these lower vertebrates do. We hope that elucidating the molecular mechanisms that lower vertebrates use to regulate regeneration will one day result in therapies aimed at activating regenerative potential in human organs.

Adult zebrafish efficiently regenerate many organs and structures after injury.

Fin regeneration
We use the zebrafish model to study the signaling pathways and the genetic regulatory circuits that regulate fin and heart regeneration. The fin is a great, simple model for studying basic cellular and molecular mechanisms of regeneration. We have found that Wnt signaling pathways play important roles in regulating fin regeneration. In particular, Wnt/beta-catenin signaling is required for formation and proliferation of the blastema, a population of stem cell-like progenitor cells that gives rise to all cell types of the regenerating fin. In contrast, beta-catenin independent Wnt signaling appears to inhibit regeneration. Currently, we are attempting to learn more about the function of these pathways in fin regeneration by identification of downstream signaling components, identification and knockdown of target genes, and by high resolution live imaging techniques.

Wnt/beta-catenin signaling is required for zebrafish fin regeneration.

Wnt pathway mediators and modulators
The Wnt/beta-catenin signaling pathway is of enormous importance for the regulation of animal cell fate and proliferation during many processes in embryonic development and in the function of adult stem cells. However, in many contexts it is unclear how Wnt signaling mediates these effects, since few direct targets genes of the pathway are known. We are therefore interested in identifying genes that are regulated by Wnt/beta-catenin signaling not only during fin regeneration, but during embryogenesis as well. Genes that are regulated by Wnt signaling in many tissues are likely to represent feedback modulators of the pathway. We have identified several of these general Wnt targets and are studying their function during embryogenesis and during adult fin regeneration.

Zebrafish transgenic for heatshock-inducible inhibitors (hsDkk1GFP) or activators (hsWnt8GFP) of Wnt/beta-catenin signaling are ideal tools to study the roles of the Wnt signaling network at any timepoint during embryonic development or in adults.

Heart regeneration
Heart damage, usually caused by infarction, is a leading cause of death in humans. After cardiomyocyte death the damaged part of the myocard in humans undergoes extensive scarring and fibrosis, and no new cardiomyocytes are produced. Thus, infarction results in permanent damage to the heart. In contrast, zebrafish are able to regenerate their hearts without scarring. After amputation of up to 20% of the ventricle, the lost tissue is replaced with newly differentiating cardiomyocytes within 30 days. Currently, the molecular mechanisms regulating the formation and proliferation of progenitor cells that drive heart regeneration are completely unknown. We have found that Wnt/beta-catenin signaling is activated early during regeneration. Using transgenic zebrafish lines, we currently investigate the function of Wnt signaling in heart regeneration.

Zebrafish hearts regenerate. Within 30 days after resection of the tip of the ventricle, the blood clot sealing the wound disappears (arrows) and no scar remains.

2008
Wolfram Goessling, Trista E. North, Allegra M. Lord, Craig Ceol, Sang Lee, Gilbert Weidinger, Caitlin Bourque, Robbert Strijbosch, Anna-Pavlina Haramis, Mark Puder, Hans Clevers, Randall T. Moon and Leonard I. Zon (2008). APC mutant zebrafish uncover a changing temporal requirement for Wnt signaling in liver development. Developmental Biology 320, 161-74.

Karen A. McFarland, Jolanta M. Topczewska, Gilbert Weidinger, Richard I. Dorsky and Bruce Appel (2008). Hh and Wnt signaling regulate formation of olig2+ neurons in the zebrafish cerebellum. Developmental Biology 318, 162-171.

Elly M. Tanaka and Gilbert Weidinger (2008). Micromanaging regeneration. Genes & Development 22, 700-705.

Elly M. Tanaka and Gilbert Weidinger (2008). Heads or Tails-Can Wnt tell which one is up? Nature Cell Biology 10, 122-124.

Jennifer Bonner, Suzanna L Gribble, Eric S Veien, Oliver B Nikolaus, Gilbert Weidinger and Richard I Dorsky (2008). Proliferation and patterning are mediated independently in the dorsal spinal cord downstream of canonical Wnt signaling. Developmental Biology 313, 398-407.

2007
"Gilbert Weidinger: Regeneration researcher". Interviewed by Ruth Williams. (2007) J. Cell Biology 179, 1088-1089.

Yukio Nakamura, Gilbert Weidinger, Jennifer O. Liang, Allisan Aquilina-Beck, Keiko Tamai, Randall T. Moon, and Matthew L. Warman (2007). Modulation of Wnt and BMP signaling by the CCN family member Wisp3. J. Clinical Investigation 117, 3075-86.

Cristi L. Stoick-Cooper, Randall T. Moon, and Gilbert Weidinger (2007). Advances in signaling in vertebrate regeneration as a prelude to regenerative medicine. Genes & Development21, 1292-1315.

Gilbert Weidinger*, Shuichi Ueno*, Tomoaki Osugi*, Aimee D. Kohn, Jonathan L. Golob, Lil Pabon, Hans Reinecke, Randall T. Moon and Charles E. Murry (2007). Biphasic Role for Wnt/β-catenin signaling in cardiac specification in zebrafish and embryonic stem cells. PNAS 104, 9685-9690.
* equal contribution

this paper was featured in a commentary by Kausalia Vijayaragavan, and Mickie Bhatia (2007): "Early cardiac development: A Wnt beat away" PNAS 104, 9549-9550.

this paper was also featured in a preview by Tzahor E. (2007): "Wnt/beta-Catenin Signaling and Cardiogenesis: Timing Does Matter." Developmental Cell 13, 10-13.

Gilbert Weidinger*, Cristi L. Stoick-Cooper*, Kim Riehle, Michael B. Major, Nelson Fausto, and Randall T. Moon (2007). Wnt signaling pathways have opposing roles in organ regeneration. Development 134, 479-489.
* equal contribution

see news stories on this publication in:
Howard Hughes Medical Institute News
Redorbit.com

2005
Gilbert Weidinger, Chris Thorpe, Katrin Wuennenberg-Stapleton, John Ngai, and Randall T. Moon (2005). The Sp1-related transcription factor sp5l acts downstream of Wnt/β:-catenin signaling in mesoderm and neuroectoderm patterning. Current Biology 15, 489-500.

Chris Thorpe, Gilbert Weidinger, and Randall T. Moon (2005). Wnt/β:-catenin regulation of the Sp1-related transcription factor sp5l promotes tail development in zebrafish. Development 132, 1763-1772

2003
Gilbert Weidinger, and Randall T. Moon (2003). When Wnts antagonize Wnts. Journal of Cell Biology 162, 753-5.

Gilbert Weidinger, Jürg Stebler, Krasimir Slanchev, Karin Dumstrei, Clare Wise, Robin Lovell-Badge, Christine Thisse, Bernard Thisse, and Erez Raz (2003): dead end, a novel vertebrate germ plasm component, is required for zebrafish primordial germ cell migration and survival. Current Biology 13, 1429-1434

2002
Brian Ciruna, Gilbert Weidinger, Holger Knaut, Bernard Thisse, Christine Thisse, Erez Raz, and Alexander F. Schier (2002): Production of maternal-zygotic mutant zebrafish by germ-line replacement. PNAS 99, 14919-14924

Gilbert Weidinger, Uta Wolke, Christine Thisse, Bernard Thisse & Erez Raz (2002): Regulation of zebrafish primordial germ cell migration by attraction towards an intermediate target. Development 129, 25-36.

Uta Wolke, Gilbert Weidinger, Marion Köprunner & Eraz Raz (2002): Multiple levels of post-transcriptional control lead to germ line specific gene expression in the zebrafish. Current Biology 12, 289-294.

1999
Gilbert Weidinger*, Uta Wolke*, Marion Köprunner, Michael Klinger & Erez Raz (1999): Identification of tissues and patterning events required for distinct steps in early migration of zebrafish primordial germ cells. Development 126, 5295-5307.
* equal contribution

1998
Fritz Aberger, Gilbert Weidinger, Horst Grunz & Klaus Richter (1998). Anterior specification of embryonic ectoderm: the role of the Xenopus cement gland-specific gene XAG-2. Mechanisms of Development 72, 115-130.

1997
Fritz Aberger, Gilbert Weidinger & Klaus Richter (1997): A member of the Met/HGF-receptor family is expressed in a BMP-4-like pattern in the ectoderm of Xenopus gastrulae. Biochemical & Biophysical Research Communications 231, 191-195.

The main funding for our group is provided by the Deutsche Forschungsgemeinschaft (DFG) as part of the Collaborative Research Center (Sonderforschungsbereich 655) "Cells into Tissues"


We also receive funding by the German ministry for Science and Education (BMBF) as part of the Consortium "Regenerative potential of mesenchymal stem cells".

Our group has also been granted financial support by the Deutsche Stiftung für Herzforschung.

We are member of the Center for Regenerative Therapies Dresden, from which we receive funding as well.

Furthermore, we participate in the Dresden International Graduate School for Biomedicine and Bioengeneering.

At the moment there are no open positions in our group.