PUBLICATION

Pdlim7 (LMP4) regulation of Tbx5 specifies zebrafish heart atrio-ventricular boundary and valve formation

Authors
Camarata, T., Krcmery, J., Snyder, D., Park, S., Topczewski, J., and Simon, H.G.
ID
ZDB-PUB-091120-30
Date
2010
Source
Developmental Biology   337(2): 233-245 (Journal)
Registered Authors
Topczewski, Jacek
Keywords
Pdlim7, Tbx5, PDZ-LIM, T-box, heart, Atrio-ventricular boundary
MeSH Terms
  • Heart Valves/embryology*
  • Heart Valves/metabolism
  • T-Box Domain Proteins/genetics
  • T-Box Domain Proteins/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Animals
  • Gene Expression Regulation, Developmental
  • Chlorocebus aethiops
  • Embryonic Development/genetics
  • Gene Knockdown Techniques
  • Adaptor Proteins, Signal Transducing/genetics
  • Adaptor Proteins, Signal Transducing/metabolism*
  • Cell Differentiation
  • Animal Structures/metabolism
  • Organ Specificity/genetics
  • Protein Binding
  • Body Patterning*/genetics
  • Heart Ventricles/embryology*
  • Heart Ventricles/metabolism
  • Myocardium/cytology
  • Myocardium/metabolism
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism
  • Heart Atria/embryology*
  • Heart Atria/metabolism
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • COS Cells
  • Time Factors
(all 30)
PubMed
19895804 Full text @ Dev. Biol.
Abstract
Tbx5 is involved in congenital heart disease, however, the mechanisms leading to organ malformation are greatly unknown. We hypothesized a model by which the Tbx5 binding protein Pdlim7 controls nuclear/cytoplasmic shuttling and function of the transcription factor. Using the zebrafish, we present in vivo significance for an essential role of Tbx5/Pdlim7 protein interaction in the regulation of cardiac formation. Knock-down of Pdlim7 results in a non-looped heart, strikingly reminiscent of the tbx5 heartstrings mutant phenotype. However, while misregulation of Pdlim7 and Tbx5 produce similar aberrant cardiac morphology, molecular and histological analysis uncovered that the Pdlim7 and Tbx5 cardiac phenotypes are due to opposite effects on valve development. Loss of Pdlim7 function causes no valve tissue to develop while lack of Tbx5 results in increased valve tissue. These opposing defects are evident before valve formation and are the result of distinct gene misregulation during specification of the atrio-ventricular (AV) boundary. We show that Pdlim7/Tbx5 interactions affect the expression of Tbx5 target genes nppa and tbx2b at the AV boundary, and their domains of misexpression directly correlate with the identified valve defects. These studies demonstrate that controlling the correct balance of Tbx5 activity is crucial for the specification of the AV boundary and valve formation.
Genes / Markers
Figures
Figure Gallery (13 images) / 2
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WT + MO3-pdlim7standard conditionsPrim-5
WT + MO3-pdlim7standard conditionsPrim-5
WT + MO3-pdlim7standard conditionsPrim-5
WT + MO3-pdlim7standard conditionsPrim-5
WT + MO3-pdlim7standard conditionsLong-pec
WT + MO3-pdlim7standard conditionsLong-pec
WT + MO3-pdlim7standard conditionsLong-pec
WT + MO3-pdlim7standard conditionsLong-pec
WT + MO3-pdlim7standard conditionsLong-pec
WT + MO3-pdlim7standard conditionsLong-pec
1 - 10 of 67
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
m21
    		Point Mutation
    1 - 1 of 1
    Show
    Human Disease / Model
    Human Disease Fish Conditions Evidence
    congenital heart diseaseTAS
    1 - 1 of 1
    Show
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    pdlim7MO3-pdlim7MRPHLNO
    pdlim7MO4-pdlim7MRPHLNO
    tp53MO4-tp53MRPHLNO
    1 - 3 of 3
    Show
    Fish
    Fish
    tbx5am21/m21
    tbx5am21/+
    tbx5am21/+ + MO4-pdlim7
    WT
    WT + MO3-pdlim7
    WT + MO3-pdlim7 + MO4-pdlim7
    WT + MO4-pdlim7
    WT + MO4-pdlim7 + MO4-tp53
    1 - 8 of 8
    Show
    Antibodies
    Orthology
    Gene Orthology
    pdlim7
    1 - 1 of 1
    Show
    Engineered Foreign Genes
    No data available
    Mapping
    No data available
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    Citation
    Camarata, T., Krcmery, J., Snyder, D., Park, S., Topczewski, J., and Simon, H.G. (2010) Pdlim7 (LMP4) regulation of Tbx5 specifies zebrafish heart atrio-ventricular boundary and valve formation. Developmental Biology. 337(2):233-245.