Chromatin Remodeling Complexes in Heart Valve development

Maithri SarangamSummer 2012Stankunas Lab

BAF Chromatin remodeling complex

Heart Valves

Significance• Congenital heart valve defects affect significant portion of the

world population.

• Bicuspid aortic valve, affects about 2% all people.

• greatly increases risk for: ventricular hypertrophy and dilation, causing heart failure, aortic aneurysms, and issues with coronary vasculature

Conditional knockout of Brg1NFATc1:Cre; BrgF/F

NFATc1:Cre; Brg F/+ (Wildtype) NFATc1:Cre; Brg F/F (Mutant)

E14.5 Aortic valve phenotype

• Embryos harvested at E14.5

• “Thickened” leaflets

• Misshapen

• Accompanied by other defects such as VSD and misshapen pulmonic valves

16.5 valve 3D reconstruction

3D reconstruction • There is a partial fusion

of leaflets 2 and 3.

• There is an increase in volume that was not observed in the other phenotype

• Still unclear why there seem to be different phenotypes.

Mutant survival at 16.5

• Totals:– 142 embryos, 131 live, 24 live mutants, 8 dead

mutants

• Frequencies:– Theoretical mutant frequency: 25%– Actual mutant frequency: 18.3% – = 25.0%

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Molecular basis

Molecular Basis

Next Steps

• Continue to explore the molecular basis of the phenotype, in embryonic mice, and adult mice.

• Continue to examine matrix proteins, and transcription factors.

Thank You!

• Professor Kryn Stankunas• Brynn Simek• Stankunas Lab

– Fern Bosada– Vidusha Devasthali– Ben Smood– Alex Akerberg– Cho Li– Alan Gomez– Scott Stewart