title: The mouse Wnt/PCP protein Vangl2 is necessary for migration of facial branchiomotor neurons, and functions independently of Dishevelled.
abstract: During development, facial branchiomotor (FBM) neurons, which innervate muscles in the vertebrate head, migrate caudally and radially within the brainstem to form a motor nucleus at the pial surface. Several components of the Wnt/planar cell polarity (PCP) pathway, including the transmembrane protein Vangl2, regulate caudal migration of FBM neurons in zebrafish, but their roles in neuronal migration in mouse have not been investigated in detail. Therefore, we analyzed FBM neuron migration in mouse looptail (Lp) mutants, in which Vangl2 is inactivated. In Vangl2(Lp/+) and Vangl2(Lp/Lp) embryos, FBM neurons failed to migrate caudally from rhombomere (r) 4 into r6. Although caudal migration was largely blocked, many FBM neurons underwent normal radial migration to the pial surface of the neural tube. In addition, hindbrain patterning and FBM progenitor specification were intact, and FBM neurons did not transfate into other non-migratory neuron types, indicating a specific effect on caudal migration. Since loss-of-function in some zebrafish Wnt/PCP genes does not affect caudal migration of FBM neurons, we tested whether this was also the case in mouse. Embryos null for Ptk7, a regulator of PCP signaling, had severe defects in caudal migration of FBM neurons. However, FBM neurons migrated normally in Dishevelled (Dvl) 1/2 double mutants, and in zebrafish embryos with disrupted Dvl signaling, suggesting that Dvl function is essentially dispensable for FBM neuron caudal migration. Consistent with this, loss of Dvl2 function in Vangl2(Lp/+) embryos did not exacerbate the Vangl2(Lp/+) neuronal migration phenotype. These data indicate that caudal migration of FBM neurons is regulated by multiple components of the Wnt/PCP pathway, but, importantly, may not require Dishevelled function. Interestingly, genetic-interaction experiments suggest that rostral FBM neuron migration, which is normally suppressed, depends upon Dvl function.
authors: Division of Biological Sciences, Bond Life Sciences Center, University of Missouri, Columbia, 65211, USA.
authors: Derrick M
authors: DM
authors: Glasco
authors: Vinoth
authors: V
authors: Sittaramane
authors: Whitney
authors: W
authors: Bryant
authors: Bernd
authors: B
authors: Fritzsch
authors: Anagha
authors: A
authors: Sawant
authors: Anju
authors: A
authors: Paudyal
authors: Michelle
authors: M
authors: Stewart
authors: Philipp
authors: P
authors: Andre
authors: Gonçalo
authors: G
authors: Cadete Vilhais-Neto
authors: Yingzi
authors: Y
authors: Yang
authors: Mi-Ryoung
authors: MR
authors: Song
authors: Jennifer N
authors: JN
authors: Murdoch
authors: Anand
authors: A
authors: Chandrasekhar
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D016764:Cell Polarity; D000072261:Dishevelled Proteins; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008959:Models, Neurological; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology*; D009415:Nerve Net / Q000166:cytology / Q000196:embryology / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology; D060449:Wnt Signaling Pathway; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; C000606579:Dvl1 protein, mouse; C000606582:Dvl2 protein, mouse; C431577:Ltap protein, mouse; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; C486452:Ptk7 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases