PUBLICATION

Smad4 controls signaling robustness and morphogenesis by differentially contributing to the Nodal and BMP pathways

Authors
Guglielmi, L., Heliot, C., Kumar, S., Alexandrov, Y., Gori, I., Papaleonidopoulou, F., Barrington, C., East, P., Economou, A.D., French, P.M.W., McGinty, J., Hill, C.S.
ID
ZDB-PUB-211106-4
Date
2021
Source
Nature communications   12: 6374 (Journal)
Registered Authors
Hill, Caroline
Keywords
none
Datasets
GEO:GSE162289, GEO:GSE164574
MeSH Terms
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/growth & development*
  • Zebrafish/metabolism
  • Bone Morphogenetic Proteins/metabolism*
  • Smad4 Protein/deficiency
  • Smad4 Protein/genetics
  • Smad4 Protein/metabolism*
  • Embryonic Development
  • Transforming Growth Factor beta/metabolism*
  • Endoderm/metabolism
  • Nodal Protein/metabolism*
  • Gene Knockout Techniques
  • Signal Transduction
  • Animals
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Mesoderm/metabolism
  • Morphogenesis
(all 20)
PubMed
34737283 Full text @ Nat. Commun.
Abstract
The transcriptional effector SMAD4 is a core component of the TGF-β family signaling pathways. However, its role in vertebrate embryo development remains unresolved. To address this, we deleted Smad4 in zebrafish and investigated the consequences of this on signaling by the TGF-β family morphogens, BMPs and Nodal. We demonstrate that in the absence of Smad4, dorsal/ventral embryo patterning is disrupted due to the loss of BMP signaling. However, unexpectedly, Nodal signaling is maintained, but lacks robustness. This Smad4-independent Nodal signaling is sufficient for mesoderm specification, but not for optimal endoderm specification. Furthermore, using Optical Projection Tomography in combination with 3D embryo morphometry, we have generated a BMP morphospace and demonstrate that Smad4 mutants are morphologically indistinguishable from embryos in which BMP signaling has been genetically/pharmacologically perturbed. Smad4 is thus differentially required for signaling by different TGF-β family ligands, which has implications for diseases where Smad4 is mutated or deleted.
Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
fci101
    Small Deletion
    tdc24
      Point Mutation
      tz257
        Point Mutation
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        smad4aCRISPR1-smad4aCRISPR
        smad4bMO1-smad4bMRPHLNO
        1 - 2 of 2
        Show
        Fish
        Antibodies
        Name Type Antigen Genes Isotypes Host Organism
        Ab2-mcm6monoclonal
          IgG2aMouse
          Ab4-smad2/3
            IgG1Mouse
            Ab4-smad4monoclonal
              IgG1Mouse
              Ab4-smad5polyclonal
                IgGRabbit
                Ab9-smad2monoclonal
                  IgGRabbit
                  Ab11-smad2
                    IgGRabbit
                    Ab13-smadmonoclonal
                      IgGRabbit
                      1 - 7 of 7
                      Show
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      No data available
                      Mapping
                      No data available