title: The neuroepithelial basement membrane serves as a boundary and a substrate for neuron migration in the zebrafish hindbrain.
abstract: BACKGROUND
  The facial branchiomotor neurons of cranial nerve VII undergo a stereotyped tangential migration in the zebrafish hindbrain that provides an ideal system for examining the complex interactions between neurons and their environment that result in directed migration. Several studies have shown the importance of the planar cell polarity pathway in facial branchiomotor neuron migration but the role of apical-basal polarity has not been determined. Here we examine the role of the PAR-aPKC complex in forming the basal structures that guide facial branchiomotor neurons on an appropriate migratory path.
  
  
  RESULTS
  High resolution timelapse imaging reveals that facial branchiomotor neurons begin their migration by moving slowly ventrally and posteriorly with their centrosomes oriented medially and then, upon contact with the Laminin-containing basement membrane at the rhombomere 4-rhombomere 5 boundary, speed up and reorient their centrosomes on the anterior-posterior axis. Disruption of the PAR-aPKC complex members aPKClambda, aPKCzeta, and Pard6gb results in an ectopic ventral migration in which facial branchiomotor neurons escape from the hindbrain through holes in the Laminin-containing basement membrane. Mosaic analysis reveals that the requirement for aPKC is cell-nonautonomous, indicating that it is likely required in the surrounding polarized neuroepithelium rather than in facial motor neurons themselves. Ventral facial motor neuron ectopia can be phenocopied by mutation of lamininalpha1, suggesting that it is defects in maintenance of the laminin-containing basement membrane that are the likely cause of ventral mismigration in aPKClambda+zeta double morphants.
  
  
  CONCLUSIONS
  Our results suggest that the laminin-containing ventral basement membrane, dependent on the activity of the PAR-aPKC complex in the hindbrain neuroepithelium, is both a substrate for migration and a boundary that constrains facial branchiomotor neurons to the appropriate migratory path.
authors.affiliation: HHMI and Division of Basic Science, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109-1024, USA.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Grant
authors.forename: Cecilia B
authors.initials: CB
authors.lastname: Moens
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001485:Basement Membrane / Q000502:physiology / Q000648:ultrastructure*; D001934:Branchial Region / Q000196:embryology; D002465:Cell Movement / Q000235:genetics*; D016764:Cell Polarity / Q000502:physiology; D002828:Choristoma / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D009046:Motor Neurons / Q000502:physiology / Q000648:ultrastructure*; D018482:Muscle, Skeletal / Q000294:innervation; D009154:Mutation / Q000235:genetics; D046569:Neuroepithelial Cells / Q000502:physiology / Q000648:ultrastructure*; D010641:Phenotype; D011493:Protein Kinase C / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012249:Rhombencephalon / Q000196:embryology*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007797:Laminin; C534334:Pard6gb protein, zebrafish; D029961:Zebrafish Proteins; C510925:laminin alpha1, zebrafish; C115015:PKC-3 protein; D011493:Protein Kinase C