PUBLICATION

Regulation of left-right asymmetries in the zebrafish by Shh and BMP4

Authors
Schilling, T.F., Concordet, J.-P., and Ingham, P.W.
ID
ZDB-PUB-990607-10
Date
1999
Source
Developmental Biology   210(2): 277-287 (Journal)
Registered Authors
Ingham, Philip, Schilling, Tom
Keywords
heart; hedgehog; BMP; left-right asymmetry
MeSH Terms
  • Heart/embryology
  • Zebrafish/embryology*
  • Proto-Oncogene Proteins*
  • Trans-Activators/genetics
  • Signal Transduction
  • Homeodomain Proteins/genetics
  • Body Patterning*
  • Mesoderm/physiology
  • Bone Morphogenetic Protein 4
  • Animals
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins
  • Proteins/genetics
  • Proteins/physiology*
  • Zebrafish Proteins
  • Proto-Oncogene Protein c-fli-1
  • Bone Morphogenetic Proteins/genetics
  • Bone Morphogenetic Proteins/physiology*
  • Embryonic Induction*
  • Transcription Factors*
  • Xenopus Proteins*
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/physiology*
  • DNA-Binding Proteins/genetics
  • Viscera/embryology
(all 25)
PubMed
10357891 Full text @ Dev. Biol.
Abstract
Left-right (LR) asymmetry of the heart in vertebrates is regulated by early asymmetric signals in the embryo, including the secreted signal Sonic hedgehog (Shh), but less is known about LR asymmetries of visceral organs. Here we show that Shh also specifies asymmetries in visceral precursors in the zebrafish and that cardiac and visceral sidedness are independent. The transcription factors fli-1 and Nkx-2.5 are expressed asymmetrically in the precardiac mesoderm and subsequently in the heart; an Eph receptor, rtk2, and an adhesion protein, DM-GRASP, mark early asymmetries in visceral endoderm. Misexpression of shh mRNA, or a dominant negative form of protein kinase A, on the right side reverses the expression of these asymmetries in precursors of both the heart and the viscera. Reversals in the heart and gut are uncoordinated, suggesting that each organ interprets the signal independently. Misexpression of Bone Morphogenetic Protein (BMP4) on the right side reverses the heart, but visceral organs are unaffected, consistent with a function for BMPs locally in the heart field. Zebrafish mutants with midline defects show independent reversals of cardiac and visceral laterality. Thus, hh signals influence the development of multiple organ asymmetries in zebrafish and different organs appear to respond to a central cascade of midline signaling independently, which in the heart involves BMP4.
Genes / Markers
Figures
Figure Gallery (5 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
noton1/n1 (AB)standard conditions20-25 somites
noton1/n1 (AB)standard conditions20-25 somites
noton1/n1 (AB)standard conditionsPrim-25
noton1/n1 (AB)standard conditionsPrim-25
tdgf1m134/m134 (AB)standard conditions20-25 somites
tdgf1m134/m134 (AB)standard conditions20-25 somites
tdgf1m134/m134 (AB)standard conditionsPrim-25
tdgf1m134/m134 (AB)standard conditionsPrim-25
1 - 8 of 8
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b16
    		Deficiency
    b104
      		Indel
      b160
        		Indel
        m134
          		Point Mutation
          n1
            		Small Deletion
            ty97
              		Point Mutation
              z1
                		Deficiency
                1 - 7 of 7
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                Human Disease / Model
                No data available
                Sequence Targeting Reagents
                No data available
                Fish
                Fish
                AB
                Df(Chr10:tdgf1)z1/z1
                Df(Chr12:hhex,ndr2)b16/b16 (AB)
                noton1/n1 (AB)
                scube2ty97/ty97
                tbx16b104/b104 (AB)
                tbxtab160/b160 (AB)
                tdgf1m134/m134 (AB)
                1 - 8 of 8
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                Antibodies
                Orthology
                No data available
                Engineered Foreign Genes
                No data available
                Mapping
                No data available
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                Citation
                Schilling, T.F., Concordet, J.-P., and Ingham, P.W. (1999) Regulation of left-right asymmetries in the zebrafish by Shh and BMP4. Developmental Biology. 210(2):277-287.