PUBLICATION

The mediator complex subunit Med10 regulates heart valve formation in zebrafish by controlling Tbx2b-mediated Has2 expression and cardiac jelly formation

Authors
Just, S., Hirth, S., Berger, I.M., Fishman, M.C., Rottbauer, W.
ID
ZDB-PUB-160628-12
Date
2016
Source
Biochemical and Biophysical Research Communications   477(4): 581-8 (Journal)
Registered Authors
Berger, Ina, Fishman, Mark C., Hirth, Sophia, Just, Steffen, Rottbauer, Wolfgang
Keywords
Foxn4, Has2, Med10, Tbx2b, Valve formation, Zebrafish
MeSH Terms
  • T-Box Domain Proteins/metabolism
  • T-Box Domain Proteins/physiology*
  • Heart Valves/embryology*
  • Heart Valves/metabolism
  • Signal Transduction
  • Mutation
  • Glucuronosyltransferase/metabolism*
  • Mediator Complex/physiology*
  • Zebrafish Proteins/metabolism*
  • Zebrafish Proteins/physiology*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Animals
  • Forkhead Transcription Factors/metabolism
(all 14)
PubMed
27343557 Full text @ Biochem. Biophys. Res. Commun.
Abstract
In search for novel key regulators of cardiac valve formation, we isolated the zebrafish cardiac valve mutant ping pong (png). We find that an insertional promoter mutation within the zebrafish mediator complex subunit 10 (med10) gene is leading to impaired heart valve formation. Expression of the T-box transcription factor 2b (Tbx2b), known to be essential in cardiac valve development, is severely reduced in png mutant hearts. We demonstrate here that transient reconstitution of Tbx2b expression rescues AV canal development in png mutant zebrafish. By contrast, overexpression of Forkhead box N4 (Foxn4), a known upstream regulator of Tbx2b, is not capable to reconstitute tbx2b expression and heart valve formation in Med10-deficient png mutant hearts. Interestingly, hyaluronan synthase 2 (has2), a known downstream target of Tbx2 and producer of hyaluronan (HA) - a major ECM component of the cardiac jelly and critical for proper heart valve development - is completely absent in ping pong mutant hearts. We propose here a rather unique role of Med10 in orchestrating cardiac valve formation by mediating Foxn4 dependent tbx2b transcription, the expression of Has2 and subsequently the proper development of the cardiac jelly.
Genes / Markers
Figures
Figure Gallery (9 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
m683
    Insertion
    w34TgTransgenic Insertion
      y1TgTransgenic Insertion
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        foxn4MO2-foxn4MRPHLNO
        med10MO1-med10MRPHLNO
        med10MO3-med10MRPHLNO
        1 - 3 of 3
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        Fish
        Antibodies
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        EGFPEFGEGFP
        GFPEFGGFP
        1 - 2 of 2
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        Mapping
        No data available