title: PCP Signaling between Migrating Neurons and their Planar-Polarized Neuroepithelial Environment Controls Filopodial Dynamics and Directional Migration.
abstract: The planar cell polarity (PCP) pathway is a cell-contact mediated mechanism for transmitting polarity information between neighboring cells. PCP "core components" (Vangl, Fz, Pk, Dsh, and Celsr) are essential for a number of cell migratory events including the posterior migration of facial branchiomotor neurons (FBMNs) in the plane of the hindbrain neuroepithelium in zebrafish and mice. While the mechanism by which PCP signaling polarizes static epithelial cells is well understood, how PCP signaling controls highly dynamic processes like neuronal migration remains an important outstanding question given that PCP components have been implicated in a range of directed cell movements, particularly during vertebrate development. Here, by systematically disrupting PCP signaling in a rhombomere-restricted manner we show that PCP signaling is required both within FBMNs and the hindbrain rhombomere 4 environment at the time when they initiate their migration. Correspondingly, we demonstrate planar polarized localization of PCP core components Vangl2 and Fzd3a in the hindbrain neuroepithelium, and transient localization of Vangl2 at the tips of retracting FBMN filopodia. Using high-resolution timelapse imaging of FBMNs in genetic chimeras we uncover opposing cell-autonomous and non-cell-autonomous functions for Fzd3a and Vangl2 in regulating FBMN protrusive activity. Within FBMNs, Fzd3a is required to stabilize filopodia while Vangl2 has an antagonistic, destabilizing role. However, in the migratory environment Fzd3a acts to destabilize FBMN filopodia while Vangl2 has a stabilizing role. Together, our findings suggest a model in which PCP signaling between the planar polarized neuroepithelial environment and FBMNs directs migration by the selective stabilization of FBMN filopodia.
authors.affiliation: Division of Basic Science, Fred Hutchinson Cancer Research Center, and University of Washington Molecular and Cellular Biology Graduate Program, Seattle, Washington, United States of America.
authors.forename: Crystal F
authors.initials: CF
authors.lastname: Davey
authors.affiliation: Division of Basic Science, Fred Hutchinson Cancer Research Center, and University of Washington Molecular and Cellular Biology Graduate Program, Seattle, Washington, United States of America.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Mathewson
authors.affiliation: Division of Basic Science, Fred Hutchinson Cancer Research Center, and University of Washington Molecular and Cellular Biology Graduate Program, Seattle, Washington, United States of America.
authors.forename: Cecilia B
authors.initials: CB
authors.lastname: Moens
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics*; D016764:Cell Polarity / Q000235:genetics*; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism; D046569:Neuroepithelial Cells / Q000378:metabolism; D011554:Pseudopodia / Q000235:genetics* / Q000378:metabolism; D012249:Rhombencephalon / Q000254:growth & development* / Q000378:metabolism; D015398:Signal Transduction; D015027:Zebrafish