title: Planar polarity pathway and Nance-Horan syndrome-like 1b have essential cell-autonomous functions in neuronal migration.
abstract: Components of the planar cell polarity (PCP) pathway are required for the caudal tangential migration of facial branchiomotor (FBM) neurons, but how PCP signaling regulates this migration is not understood. In a forward genetic screen, we identified a new gene, nhsl1b, required for FBM neuron migration. nhsl1b encodes a WAVE-homology domain-containing protein related to human Nance-Horan syndrome (NHS) protein and Drosophila GUK-holder (Gukh), which have been shown to interact with components of the WAVE regulatory complex that controls cytoskeletal dynamics and with the polarity protein Scribble, respectively. Nhsl1b localizes to FBM neuron membrane protrusions and interacts physically and genetically with Scrib to control FBM neuron migration. Using chimeric analysis, we show that FBM neurons have two modes of migration: one involving interactions between the neurons and their planar-polarized environment, and an alternative, collective mode involving interactions between the neurons themselves. We demonstrate that the first mode of migration requires the cell-autonomous functions of Nhsl1b and the PCP components Scrib and Vangl2 in addition to the non-autonomous functions of Scrib and Vangl2, which serve to polarize the epithelial cells in the environment of the migrating neurons. These results define a role for Nhsl1b as a neuronal effector of PCP signaling and indicate that proper FBM neuron migration is directly controlled by PCP signaling between the epithelium and the migrating neurons.
authors.affiliation: Howard Hughes Medical Institute and Division of Basic Science, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Walsh
authors.forename: Paul K
authors.initials: PK
authors.lastname: Grant
authors.forename: John A
authors.initials: JA
authors.lastname: Morgan
authors.forename: Cecilia B
authors.initials: CB
authors.lastname: Moens
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D005154:Facial Nerve / Q000166:cytology*; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000378:metabolism*; D016296:Mutagenesis; D009474:Neurons / Q000502:physiology*; D010957:Plasmids / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; C560902:Nhsl1b protein, zebrafish; D029961:Zebrafish Proteins; C502707:scrib protein, zebrafish; C491759:vangl2 protein, zebrafish