PUBLICATION

Zebrafish Prickle1b mediates facial branchiomotor neuron migration via a farnesylation-dependent nuclear activity

Authors
Mapp, O.M., Walsh, G.S., Moens, C.B., Tada, M., and Prince, V.E.
ID
ZDB-PUB-110518-43
Date
2011
Source
Development (Cambridge, England)   138(10): 2121-2132 (Journal)
Registered Authors
Mapp, Oni, Moens, Cecilia, Prince, Victoria E., Tada, Masazumi, Walsh, Gregory
Keywords
facial branchiomotor neurons, Prickle1b, neuronal migration, REST, farnesylation, zebrafish
MeSH Terms
  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Carrier Proteins/antagonists & inhibitors
  • Carrier Proteins/genetics
  • Carrier Proteins/metabolism*
  • Cell Movement
  • Cell Nucleus/metabolism
  • DNA, Complementary/genetics
  • Farnesyltranstransferase/metabolism
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Hydroxymethylglutaryl CoA Reductases/metabolism
  • LIM Domain Proteins
  • Models, Biological
  • Molecular Sequence Data
  • Motor Neurons/cytology
  • Motor Neurons/metabolism
  • Mutation
  • Neurogenesis
  • Protein Prenylation
  • Repressor Proteins/genetics
  • Repressor Proteins/metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
21521740 Full text @ Development
Abstract
The facial branchiomotor neurons (FBMNs) undergo a characteristic tangential migration in the vertebrate hindbrain. We previously used a morpholino knockdown approach to reveal that zebrafish prickle1b (pk1b) is required for this migration. Here we report that FBMN migration is also blocked in a pk1b mutant with a disruption in the consensus farnesylation motif. We confirmed that this lipid modification is required during FBMN migration by disrupting the function of farnesyl biosynthetic enzymes. Furthermore, farnesylation of a tagged Pk1b is required for its nuclear localization. Using a unique rescue approach, we have demonstrated that Pk1b nuclear localization and farnesylation are required during FBMN migration. Our data suggest that Pk1b acts at least partially independently of core planar cell polarity molecules at the plasma membrane, and might instead be acting at the nucleus. We also found that the neuronal transcriptional silencer REST is necessary for FBMN migration, and we provide evidence that interaction between Pk1b and REST is required during this process. Finally, we demonstrate that REST protein, which is normally localized in the nuclei of migrating FBMNs, is depleted from the nuclei of Pk1b-deficient neurons. We conclude that farnesylation-dependent nuclear localization of Pk1b is required to regulate REST localization and thus FBMN migration.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping