PUBLICATION

Tbx5-mediated expression of Ca(2+)/calmodulin-dependent protein kinase II is necessary for zebrafish cardiac and pectoral fin morphogenesis

Authors
Rothschild, S.C., Easley, C.A. 4th, Francescatto, L., Lister, J.A., Garrity, D.M., and Tombes, R.M.
ID
ZDB-PUB-090407-19
Date
2009
Source
Developmental Biology   330(1): 175-184 (Journal)
Registered Authors
Garrity, Deborah, Lister, James A., Rothschild, Sarah Chase, Tombes, Robert M.
Keywords
Tbx5, CaMK-II, Holt-Oram syndrome, Bradycardia, Heart development, Pectoral fins
MeSH Terms
  • Embryo, Nonmammalian/metabolism
  • Morphogenesis*/genetics
  • NIH 3T3 Cells
  • Transfection
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • T-Box Domain Proteins/metabolism*
  • Animals
  • Mice
  • Heart/embryology*
  • Heart/growth & development
  • Gene Expression Regulation, Developmental
  • Molecular Sequence Data
  • Amino Acid Sequence
  • Zebrafish/embryology*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism*
(all 17)
PubMed
19345202 Full text @ Dev. Biol.
Abstract
Mutations in the T-box transcription factor, TBX5, result in Holt-Oram syndrome (HOS), a human condition in which cardiac development is defective and forelimbs are stunted. Similarly, zebrafish tbx5 morphants and mutants (heartstrings; hst) lack pectoral fins and exhibit a persistently elongated heart that does not undergo chamber looping. Tbx5 is expressed in the developing atrium, ventricle and in pectoral fin fields, but its genetic targets are still being uncovered. In this study, evidence is provided that Tbx5 induces the expression of a specific member of the CaMK-II (the type II multifunctional Ca(2+)/calmodulin dependent protein kinase) family; this CaMK-II is necessary for proper heart and fin development. Morphants of beta2 CaMK-II (camk2b2), but not the beta1 CaMK-II (camk2b1) paralog, exhibit bradycardia, elongated hearts and diminished pectoral fin development. Normal cardiac phenotypes can be restored by ectopic cytosolic CaMK-II expression in tbx5 morphants. Like tbx5, camk2b2 is expressed in the pectoral fin and looping heart, but this expression is diminished in both tbx5 morphant and hst embryos. Conversely, the introduction of excess Tbx5 into zebrafish embryos and mouse fibroblasts doubles CaMK-II expression. We conclude that beta CaMK-II expression and activity are necessary for proper cardiac and limb morphogenesis. These findings not only identify a morphogenic target for Ca(2+) during heart development, but support implied roles for CaMK-II in adult heart remodeling.
Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WT + MO1-camk2b1standard conditionsProtruding-mouth
WT + MO1-camk2b1standard conditionsProtruding-mouth
WT + MO2-camk2b2standard conditionsProtruding-mouth
WT + MO2-camk2b2standard conditionsProtruding-mouth
WT + MO2-camk2b2standard conditionsProtruding-mouth
WT + MO2-camk2b2standard conditionsProtruding-mouth
WT + MO2-camk2b2standard conditionsProtruding-mouth
WT + MO2-camk2b2standard conditionsProtruding-mouth
WT + MO2-camk2b2standard conditionsProtruding-mouth
WT + MO2-camk2b2standard conditionsProtruding-mouth
1 - 10 of 18
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
m21
    		Point Mutation
    vc6TgTransgenic Insertion
      1 - 2 of 2
      Show
      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      Target Reagent Reagent Type
      camk2b1MO1-camk2b1MRPHLNO
      camk2b2MO1-camk2b2MRPHLNO
      camk2b2MO2-camk2b2MRPHLNO
      tbx4MO1-tbx4MRPHLNO
      tbx5aMO2-tbx5aMRPHLNO
      1 - 5 of 5
      Show
      Fish
      Fish
      tbx5am21/m21
      vc6Tg
      vc6Tg + MO2-camk2b2
      vc6Tg + MO2-tbx5a
      WT
      WT + MO1-camk2b1
      WT + MO1-tbx4
      WT + MO2-camk2b2
      WT + MO2-tbx5a
      1 - 9 of 9
      Show
      Antibodies
      No data available
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      DsRed2EFGDsRed2
      1 - 1 of 1
      Show
      Mapping
      No data available
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      Citation
      Rothschild, S.C., Easley, C.A. 4th, Francescatto, L., Lister, J.A., Garrity, D.M., and Tombes, R.M. (2009) Tbx5-mediated expression of Ca(2+)/calmodulin-dependent protein kinase II is necessary for zebrafish cardiac and pectoral fin morphogenesis. Developmental Biology. 330(1):175-184.