PUBLICATION

Neuron navigator 3a regulates liver organogenesis during zebrafish embryogenesis

Authors
Klein, C., Mikutta, J., Krueger, J., Scholz, K., Brinkmann, J., Liu, D., Veerkamp, J., Siegel, D., Abdelilah-Seyfried, S., and le Noble, F.
ID
ZDB-PUB-110511-16
Date
2011
Source
Development (Cambridge, England)   138(10): 1935-1945 (Journal)
Registered Authors
Abdelilah-Seyfried, Salim, Liu, Dong
Keywords
Neuron navigator 3a, liver development, neural guidance genes, intestinal endoderm, zebrafish
MeSH Terms
  • In Situ Hybridization
  • Liver/abnormalities
  • Liver/embryology*
  • Liver/innervation
  • Liver/metabolism*
  • Organogenesis/genetics
  • Organogenesis/physiology
  • Nerve Tissue Proteins/antagonists & inhibitors
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism*
  • Signal Transduction
  • Base Sequence
  • RNA, Antisense/genetics
  • Gene Knockdown Techniques
  • Animals
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • DNA Primers/genetics
  • Endoderm/embryology
  • Endoderm/metabolism
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Animals, Genetically Modified
  • Models, Biological
  • Intestines/embryology
  • Intestines/metabolism
  • Wnt Proteins/antagonists & inhibitors
  • Wnt Proteins/genetics
  • Wnt Proteins/metabolism
  • Gene Expression Regulation, Developmental
(all 32)
PubMed
21471154 Full text @ Development
Abstract
Endodermal organogenesis requires a precise orchestration of cell fate specification and cell movements, collectively coordinating organ size and shape. In Caenorhabditis elegans, uncoordinated-53 (unc-53) encodes a neural guidance molecule that directs axonal growth. One of the vertebrate homologs of unc-53 is neuron navigator 3 (Nav3). Here, we identified a novel vertebrate neuron navigator 3 isoform in zebrafish, nav3a, and we provide genetic evidence in loss- and gain-of-function experiments showing its functional role in endodermal organogenesis during zebrafish embryogenesis. In zebrafish embryos, nav3a expression was initiated at 22 hpf in the gut endoderm and at 40 hpf expanded to the newly formed liver bud. Endodermal nav3a expression was controlled by Wnt2bb signaling and was independent of FGF and BMP signaling. Morpholino-mediated knockdown of nav3a resulted in a significantly reduced liver size, and impaired development of pancreas and swim bladder. In vivo time-lapse imaging of liver development in nav3a morphants revealed a failure of hepatoblast movement out from the gut endoderm during the liver budding stage, with hepatoblasts being retained in the intestinal endoderm. In hepatocytes in vitro, nav3a acts as a positive modulator of actin assembly in lamellipodia and filipodia extensions, allowing cellular movement. Knockdown of nav3a in vitro impeded hepatocyte movement. Endodermal-specific overexpression of nav3a in vivo resulted in additional ectopic endodermal budding beyond the normal liver and pancreatic budding sites. We conclude that nav3a is required for directing endodermal organogenesis involving coordination of endodermal cell behavior.
Genes / Markers
Figures
Figure Gallery (18 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
pd1TgTransgenic Insertion
    s854TgTransgenic Insertion
      s870TgTransgenic Insertion
        w30TgTransgenic Insertion
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          nav3MO1-nav3MRPHLNO
          nav3MO2-nav3MRPHLNO
          wnt2bbMO1-wnt2bbMRPHLNO
          1 - 3 of 3
          Show
          Fish
          Antibodies
          Orthology
          Gene Orthology
          nav3
          1 - 1 of 1
          Show
          Engineered Foreign Genes
          Marker Marker Type Name
          EGFPEFGEGFP
          GFPEFGGFP
          1 - 2 of 2
          Show
          Mapping
          No data available