Original Article

Colocalization and Redistribution of Dishevelled and Actin during Wnt-induced Mesenchymal Morphogenesis

Correspondence to: W. James Nelson, Department of Molecular and Cellular Physiology, 279 Campus Dr., Box 5345, Stanford University School of Medicine, Stanford, CA 94305-5345. Tel:(650) 725-7596 Fax:(650) 498-5286 E-mail:wjnelson{at}leland.stanford.edu.

Activation of the Wnt signaling pathway is important for induction of gene expression and cell morphogenesis throughout embryonic development. We examined the subcellular localization of dishevelled, the immediate downstream component from the Wnt receptor, in the embryonic mouse kidney. Using immunofluorescence staining, confocal microscopy, and coimmunoprecipitation experiments, we show that dishevelled associates with actin fibers and focal adhesion plaques in metanephric mesenchymal cells. Stimulation of Wnt signaling leads to profound changes in metanephric mesenchymal cell morphology, including disruption of the actin cytoskeleton, increased cell spreading, and increased karyokinesis. Upon activation of Wnt signaling, dishevelled also accumulates in and around the nucleus. Casein kinase I colocalizes with dishevelled along actin fibers and in the perinuclear region, whereas axin and GSK-3 are only present around the nucleus. These data indicate a branched Wnt signaling pathway comprising a canonical signal that targets the nucleus and gene expression, and another signal that targets the cytoskeleton and regulates cell morphogenesis.

Key Words: cytoskeleton, signaling, receptor, kidney, epithelia

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