PUBLICATION

Essential and overlapping roles for laminin alpha chains in notochord and blood vessel formation

Authors
Pollard, S.M., Parsons, M.J., Kamei, M., Kettleborough, R.N., Thomas, K.A., Pham, V.N., Bae, M.K., Scott, A., Weinstein, B.M., and Stemple, D.L.
ID
ZDB-PUB-051207-18
Date
2006
Source
Developmental Biology   289(1): 64-76 (Journal)
Registered Authors
Kamei, Makoto, Kettleborough, Ross, Parsons, Michael, Pham, Van, Scott, Annabelle, Stemple, Derek L., Thomas, Kevin, Weinstein, Brant M.
Keywords
Laminin, Notochord, Blood vessels, Basement membrane, Cell differentiation
MeSH Terms
  • Laminin/genetics
  • Laminin/physiology*
  • Notochord/blood supply*
  • Notochord/embryology*
  • Endothelial Cells/cytology
  • Endothelial Cells/physiology
  • Cell Movement
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • RNA, Messenger/analysis
  • RNA, Messenger/metabolism
  • Mutation
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
  • Animals
  • Neovascularization, Physiologic*
  • Blood Vessels/chemistry
  • Blood Vessels/embryology
(all 18)
PubMed
16321372 Full text @ Dev. Biol.
Abstract
Laminins are major constituents of basement membranes and have wide ranging functions during development and in the adult. They are a family of heterotrimeric molecules created through association of an alpha, beta and gamma chain. We previously reported that two zebrafish loci, grumpy (gup) and sleepy (sly), encode laminin beta1 and gamma1, which are important both for notochord differentiation and for proper intersegmental blood vessel (ISV) formation. In this study we show that bashful (bal) encodes laminin alpha1 (lama1). Although the strongest allele, bal(m190), is fully penetrant, when compared to gup or sly mutant embryos, bal mutants are not as severely affected, as only anterior notochord fails to differentiate and ISVs are unaffected. This suggests that other alpha chains, and hence other isoforms, act redundantly to laminin 1 in posterior notochord and ISV development. We identified cDNA sequences for lama2, lama4 and lama5 and disrupted the expression of each alone or in mutant embryos also lacking laminin alpha1. When expression of laminin alpha4 and laminin alpha1 are simultaneously disrupted, notochord differentiation and ISVs are as severely affected as sly or gup mutants. Moreover, live imaging of transgenic embryos expressing enhanced green fluorescent protein in forming ISVs reveals that the vascular defects in these embryos are due to an inability of ISV sprouts to migrate correctly along the intersegmental, normally laminin-rich regions.
Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
m189
    Point Mutation
    m190
      Point Mutation
      m466
        Point Mutation
        y1TgTransgenic Insertion
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          lama1MO1-lama1MRPHLNO
          lama1MO2-lama1MRPHLNO
          lama1MO3-lama1MRPHLNO
          lama1MO4-lama1MRPHLNO
          lama2MO1-lama2MRPHLNO
          lama4MO1-lama4MRPHLNO
          lama4MO2-lama4MRPHLNO
          lama4MO3-lama4MRPHLNO
          lama5MO2-lama5MRPHLNO
          lama5MO1-lama5MRPHLNO
          1 - 10 of 10
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          Fish
          Antibodies
          Orthology
          Engineered Foreign Genes
          No data available
          Mapping