Neurobiology and Anatomy

E-mail: piotrowski @neuro.utah.edu
Address: MREB 401
Phone: 587-7638

A chemical screen to identify small molecules that rescue collective cell migration in apc mutant embryos

We are studying how populations of cells migrate using the relatively simple and accessible zebrafish sensory lateral line as a model. By analyzing the apc mutation we have uncovered that localized beta-catenin activation in a few leader cells leads to upregulation of Fgf signaling in the trailing cells, which in turn prevents b-Catenin activation in the trailing cells. Our data has also demonstrated that b-Catenin expressing leader cells inform the directional migration of the primordium via differential regulation of two chemokine receptors (unpublished). In addition to contributing to our understanding of the molecular mechanisms underlying collective cell migration during normal morphogenesis, the results from our studies also bear significance for our understanding of how these signaling pathways are involved in the collective migration of cancer cells. Both b-Catenin signaling and chemokine signaling pathways are well known to be involved in cancer progression, however we provide the first in vivo evidence that these pathway are linked. We are looking for an interested researcher to perform a chemical screen to identify small molecules which rescue cell migration in the apc mutant lateral line. The strength of the lateral line system is that it is easily visible in a transgenic zebrafish line, allowing us to rapidly screen for rescue in vivo. An additional advantage is that we have elucidated the molecular signaling pathways that are affected in apc mutants which will enable us to identify which pathways are targeted by small molecules that improve the phenotype. Thus, the apc mutant lateral line provides us with a fantastic tool to identify novel reagents that could be developed into therapeutic tools to treat the progression of certain cancers in the future.

1/2008