PUBLICATION

Enhanced canonical Wnt signaling during early zebrafish development perturbs the interaction of cardiac mesoderm and pharyngeal endoderm and causes thyroid specification defects

Authors
Vandernoot, I., Haerlingen, B., Gillotay, P., Trubiroha, A., Janssens, V., Opitz, R., Costagliola, S.
ID
ZDB-PUB-200812-1
Date
2020
Source
Thyroid : official journal of the American Thyroid Association   31(3): 420-438 (Journal)
Registered Authors
Costagliola, Sabine, Gillotay, Pierre, Haerlingen, Benoit, Janssens, Véronique, Opitz, Robert, Trubiroha, Achim, Vandernoot, Isabelle
Keywords
none
MeSH Terms
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Endoderm/abnormalities
  • Endoderm/metabolism
  • Animals, Genetically Modified
  • Morpholinos/genetics
  • Morpholinos/metabolism
  • Cytoskeletal Proteins/genetics
  • Cytoskeletal Proteins/metabolism*
  • Embryonic Development
  • Gene Expression Regulation, Developmental
  • Myocytes, Cardiac/metabolism*
  • Myocytes, Cardiac/pathology
  • Bone Morphogenetic Protein 2/genetics
  • Bone Morphogenetic Protein 2/metabolism*
  • Thyroid Gland/abnormalities
  • Thyroid Gland/metabolism*
  • Heart Defects, Congenital/genetics
  • Heart Defects, Congenital/metabolism*
  • Heart Defects, Congenital/pathology
  • Thyroid Dysgenesis/genetics
  • Thyroid Dysgenesis/metabolism*
  • Thyroid Dysgenesis/pathology
  • Bone Morphogenetic Protein 4/genetics
  • Bone Morphogenetic Protein 4/metabolism*
  • Wnt Signaling Pathway*
  • Mesoderm/abnormalities
  • Mesoderm/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Oligonucleotides, Antisense/genetics
  • Oligonucleotides, Antisense/metabolism
  • Wnt Proteins/genetics
  • Wnt Proteins/metabolism*
  • Animals
  • Congenital Hypothyroidism/genetics
  • Congenital Hypothyroidism/metabolism*
  • Congenital Hypothyroidism/pathology
  • Disease Models, Animal
(all 40)
PubMed
32777984 Full text @ Thyroid
Abstract
Congenital hypothyroidism (CH) due to thyroid dysgenesis is a frequent congenital endocrine disorder for which the molecular mechanisms remain unresolved in the majority of cases. This situation reflects, in part, our still limited knowledge about the mechanisms involved in the early steps of thyroid specification from the endoderm, in particular the extrinsic signaling cues that regulate foregut endoderm patterning. In this study, we used small molecules and genetic zebrafish models to characterize the role of various signaling pathways in thyroid specification.
We treated zebrafish embryos during different developmental periods with small molecule compounds known to manipulate the activity of Wnt signaling pathway and observed effects in thyroid, endoderm and cardiovascular development using whole mount in situ hybridization and transgenic fluorescent reporter models. We used the antisens morpholino technique to create a zebrafish arcadiac model. For thyroid rescue experiments, BMP pathway induction in zebrafish embryos was obtained by manipulation of heat-shock inducible transgenic lines.
Combined analyses of thyroid and cardiovascular development revealed that overactivation of Wnt signaling during early development leads to impaired thyroid specification concurrent with severe defects in the cardiac specification. When using a model of morpholino-induced blockage of cardiomyocyte differentiation, a similar correlation was observed, suggesting that defective signaling between cardiac mesoderm and endodermal thyroid precursors contributes to thyroid specification impairment. Rescue experiments through transient overactivation of BMP signaling could partially restore thyroid specification in models with defective cardiac development.
Collectively, our results indicate that BMP signaling is critically required for thyroid cell specification and identify cardiac mesoderm as a likely source of BMP signals. This article was deposited as a preprint in bioRxiv, p. 2019.12.19.880815, Dec. 2019.
Genes / Markers
Figures
No images available
Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
a9
    Complex
    fr13TgTransgenic Insertion
      ha01TgTransgenic Insertion
        ia4TgTransgenic Insertion
          s843TgTransgenic Insertion
            twu34TgTransgenic Insertion
              ulb1TgTransgenic Insertion
                w2
                  Point Mutation
                  w34TgTransgenic Insertion
                    1 - 9 of 9
                    Show
                    Human Disease / Model
                    No data available
                    Sequence Targeting Reagents
                    Target Reagent Reagent Type
                    mef2caMO3-mef2d,mef2caMRPHLNO
                    mef2dMO3-mef2d,mef2caMRPHLNO
                    1 - 2 of 2
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                    Fish
                    No data available
                    Antibodies
                    Name Type Antigen Genes Isotypes Host Organism
                    Ab1-smadpolyclonalIgGRabbit
                    1 - 1 of 1
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                    Orthology
                    No data available
                    Engineered Foreign Genes
                    Marker Marker Type Name
                    EGFPEFGEGFP
                    GFPEFGGFP
                    mCherryEFGmCherry
                    1 - 3 of 3
                    Show
                    Mapping