Topczewski Laboratory

The Topczewski laboratory investigates the mechanisms that control the morphogenetic processes of vertebrate embryos by using zebrafish as a model. Similarities in developmental programs among all vertebrates make zebrafish an excellent model for studying human diseases and development. In our work we utilize a combination of genetic analysis with embryological and molecular methods uniquely available in the zebrafish model. Our long-term goal is the identification of signaling pathways that will suggest novel candidate genes involved in human congenital abnormalities and diseases.

Current Research Projects

The main interest of the Topczewski laboratory is the developmental role of heparan sulfate proteoglycans from the glypican family. We are particularly interested in the role of Glypicans in the control of skeleton formation and patterning of the nervous system. Mutations in the glypican genes are associated with human syndromes resulting in skeleton dysplasias and frequently in mental retardation. In addition, in collaborative efforts we develop zebrafish models that could be used to study the biological basis of human diseases and test potential therapeutic applications.

The Role of Glypicans in Skeleton Development

Disruptions of glypican function severely perturb skeleton formation in humans and animal models. We investigate functions of Glypicans in the Wnt signaling pathway, controlling cell fate proliferation and behavior. We have demonstrated that zebrafish Notum1a cleaves Glypican 3 and acts as a strong antagonist of one of the Wnt-beta catenin pathway (Flowers GP et al., 2012). Normal signaling of the separate Wnt signaling pathway, Wnt-PCP, requires activity of Glypican 4. Mutations in the glypican 4 gene result in defects in cell migration during gastrulation (Topczewski J et al., 2001) and problems with chondrocyte organization in the cartilaginous elements of the skeleton (LeClair EE et al., 2009).

Characterization of the New Skeletal Mutant Line

In a forward genetic approach project we have isolated a mutant line with late onset skeletal defects. The ossification process in juvenile mutant fish is accelerated resulting in dwarfism phenotype, craniofacial malformations and frequently with scoliosis. Identification of the gene disrupted in this mutant will provide a new mechanism controlling skeleton formation in vertebrates.

The Regulation of Motor Axon Guidance

Development of the functioning nervous system depends on connecting neurons with their targets.  We have discovered that Notum 2, a predicted glypican antagonist, is important for the normal innervation of trunk muscles by the first motorneurons (Cantu JA et al., 2013). Our current study focuses on the molecular mechanisms of Notum 2 action in this process.

​Publications

List of publications indexed in PubMed​ by the Topczewski Laboratory​​

Laboratory Members

  • Rebecca A. Anderson, BS, Graduate Student, DGP
  • Margaret J. Kell, BS, Research Associate
  • Spencer T. Evans, BS, Research Associate

Contact Information 

Office Phone: 773.755.6545
Laboratory Phone: 773.755.6370