Graduate Training in Neuroscience
University of Washington
Randall T. Moon
Professor, Department of Pharmacology;
Director of the Institute for Stem Cell and Regenerative Medicine
We have principally been interested in the mechanisms which underly the formation of mesoderm and the central nervous system in vertebrate embryos. In the late 1980's the Drosophila segment polarity gene wingless, encoding a secreted intercellular signaling polypeptide, was found to be related to a mouse proto-oncogene, now named Wnt-1. Misexpression of Wnt-1 in Xenopus embryos led to the duplication of the embryonic axis--an unexpected and highly specific abnormality, which supported the likelihood that Wnt-1 was a signaling factor. These observations led us to explore the existence, expression, activities, and possible functions of the Wnt gene family in Xenopus and zebrafish, and to pursue the mechanisms by which these and other vertebrate genes related to Drosophila segment polarity genes participate in patterning within mesoderm and the central nervous system.
It is now apparent that vertebrate embryos express approximately a dozen Wnt genes during formation of mesoderm and the nervous system, that some Wnts continue to be expressed in the adult, and that these genes and their patterns of expression are highly conserved during evolution. We have focused on those Wnts expressed prior to or during gastrulation in Xenopus and zebrafish, and which are therefore candidates for being signaling factors involved in early specification of cell fate. These embryos have been particularly useful for transient expression of Wnts, enabling us to investigate whether there are distinct Wnt activities, the signal transduction pathways modulated by Wnts, the cellular targets of these signaling pathways, and how cells respond in real-time to Wnt signals to affect specific developmental processes.
Current projects in the lab focus on 1) the signal transduction pathway of Wnts, 2) cell physiological responses to Wnt signals, and 3) the roles of Wnts in embryonic processes. This last project involves both a molecular screen for zebrafish mutants, as well as analysis of how Wnt signaling specifies neural crest to become pigment cells.