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E. Perl and J. S. Waxman
Fig. 5.3 Reduction in RA promotes enlarged hearts. Diethylaminobenzaldehyde (DEAB) is a
potent, partially competitive inhibitor of aldehyde dehydrogenases. When zebrafish embryos are
treated with a low dose of DEAB (1 μM), which is sufficient to perturb Aldh1a2 function early
in development and recapitulate defects found in zebrafish aldh1a2/nls mutants, the hearts exhibit
cardiomegaly due to the effective promotion of both atrial (green) and ventricular (red) specification
Experiments with increased RA signaling corroborated this hypothesis, i.e. that
RA signaling restricts cardiac specification, rather than promoting atrial identity at the
expense of ventricular identity. Foremost, treatment of zebrafish embryos with high
concentrations of RA, which strongly posteriorizes embryos, completely eliminates
CM specification (Fig. 5.4) (Waxman and Yelon 2009), supporting the view that
RA signaling is necessary and sufficient for atrial and ventricular specification. RA
treatment was also reported to eliminate CMs in chick embryos and to inhibit CM
Fig. 5.4 Perturbing the RA signaling gradient can have independent effects on chamber specification. Depicted is a model for how varying levels of RA can affect cardiac chamber specification.
Loss of RA results in a marked expansion of both chambers. However, addition of low levels of
RA can also result in a slight expansion of both chambers. Lower-intermediate increases in RA can
promote atrial specification without affecting ventricular progenitor specification, while slightly
higher concentrations start to repress ventricular specification without affecting atrial specification.
Higher increases in RA can inhibit the specification of both atrial and ventricular cardiomyocytes,
even completely eliminating cardiac specification with the highest dosages
E. Perl and J. S. Waxman
Fig. 5.3 Reduction in RA promotes enlarged hearts. Diethylaminobenzaldehyde (DEAB) is a
potent, partially competitive inhibitor of aldehyde dehydrogenases. When zebrafish embryos are
treated with a low dose of DEAB (1 μM), which is sufficient to perturb Aldh1a2 function early
in development and recapitulate defects found in zebrafish aldh1a2/nls mutants, the hearts exhibit
cardiomegaly due to the effective promotion of both atrial (green) and ventricular (red) specification
Experiments with increased RA signaling corroborated this hypothesis, i.e. that
RA signaling restricts cardiac specification, rather than promoting atrial identity at the
expense of ventricular identity. Foremost, treatment of zebrafish embryos with high
concentrations of RA, which strongly posteriorizes embryos, completely eliminates
CM specification (Fig. 5.4) (Waxman and Yelon 2009), supporting the view that
RA signaling is necessary and sufficient for atrial and ventricular specification. RA
treatment was also reported to eliminate CMs in chick embryos and to inhibit CM
Fig. 5.4 Perturbing the RA signaling gradient can have independent effects on chamber specification. Depicted is a model for how varying levels of RA can affect cardiac chamber specification.
Loss of RA results in a marked expansion of both chambers. However, addition of low levels of
RA can also result in a slight expansion of both chambers. Lower-intermediate increases in RA can
promote atrial specification without affecting ventricular progenitor specification, while slightly
higher concentrations start to repress ventricular specification without affecting atrial specification.
Higher increases in RA can inhibit the specification of both atrial and ventricular cardiomyocytes,
even completely eliminating cardiac specification with the highest dosages