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Essential Role of Non-Canonical Wnt Signaling in Neural Crest Migration
Summary: Roberto Mayor studies how extracellular signals and intracellular factors work together to control differentiation and migration of the neural crest cells, stem cell�like cells that are able to differentiate into tissues such as neurons, muscle, skin, and bone.
The migration of neural crest cells is an elaborate process that requires delamination of cells from an epithelium and cell movement into an extracellular matrix. Our work has shown for the first time that planar cell polarity (PCP)/non-canonical Wnt signaling controls migration of neural crest cells. By using specific Dsh mutants, we show that the canonical Wnt signaling pathway is needed for neural crest induction while the non-canonical Wnt pathway is required for neural crest migration. In addition, we show a mutual inhibitory activity of canonical and non-canonical Wnt signaling on neural crest migration. Grafts of neural crest tissue expressing non-canonical Dsh mutants as well as neural crest cultured in vitro indicate that the PCP pathway works in a cell-autonomous manner to control neural crest migration. Expression analysis of non-canonical Wnt ligands and their putative receptors show that Wnt11 is expressed in tissue adjacent to neural crest cells expressing the Wnt receptor Fz7.
Furthermore, loss- and gain-of-function experiments reveal that Wnt11 plays an essential role in neural crest migration. Localized overexpression of Wnt11, engineered by grafting Wnt11-expressing cells into specific locations in the embryo, indicates that the direction of neural crest migration is influenced by the source of Wnt11. When Wnt11 was expressed opposite its normal site of expression, neural crest migration was blocked; when Wnt11 was expressed in the normal pathway of neural crest migration, cell movement into the Wnt11-positive cells was strongly promoted. Finally, time-lapse analysis of cell movement and cell protrusion in neural crest cultured in vitro shows that PCP/ Wnt11 directs formation of the lamellipodia and filopodia in the neural crest cells required for their delamination and/or migration.
Abstract from 2005 International Research Scholars Meeting
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