chromatin remodeling complexes in heart valve development maithri sarangam summer 2012 stankunas lab

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