ISOLATION AND CHARACTERIZATION OF A MOUSE HOMOLOG OF THE DROSOPHILA SEGMENT POLARITY GENE DISHEVELLED

In the Drosophila embryo dishevelled (dsh) function is required by tar get cells in order to respond to wingless (wg, the homolog of Wnt-1), demonstrating a role for dsh in Wnt signal transduction. We have isola ted a mouse homolog of the Drosophila dsh segment polarity gene. The 6 95-amino-acid protein encoded by the mouse dishevelled gene (Dvl-1) sh ares 50% identity (65% similarity) with dsh. Similarity searches of pr otein and DNA data bases revealed that Dvl-1 encodes an otherwise nove l polypeptide. While no functional motifs were identified, one region of Dvl-1 was found to be similar to a domain of discs large-1 (dig), a Drosophila tumor suppressor gene. In the embryo, Dvl-1 is expressed i n most tissues, with uniformly high levels in the central nervous syst em. From 7.5 days postcoitum Dvl-1 is expressed throughout the develop ing brain and spinal cord, including those regions expressing Wnt-1 an d En. Expression of Dvl-1 in adult mice was found to be widespread, wi th brain and testis exhibiting the highest levels. The majority of Dvl -1 expression in the adult cerebellum is in the granular cell layer, s imilar to the pattern seen for engrailed-2 (En-2). Throughout postnata l development of the brain Dvl-1 is highly expressed in areas of high neuronal cell density. (C) 1994 Academie Press, Inc.