1. Chromatin Remodeling Complexes in Heart Valve development Maithri Sarangam Summer 2012 Stankunas Lab

2. BAF Chromatin remodeling complex

3. Heart Valves

4. 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

5. Conditional knockout of Brg1 NFATc1:Cre; Brg F/F NFATc1:Cre; Brg F/+ (Wildtype) NFATc1:Cre; Brg F/F (Mutant)

6. E14.5 Aortic valve phenotype Embryos harvested at E14.5 “Thickened” leaflets Misshapen Accompanied by other defects such as VSD and misshapen pulmonic valves

7. 16.5 valve 3D reconstruction

8. 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.

9. Mutant survival at 16.5

10. Lincoln et. al, 2006 Molecular basis

11. Molecular Basis

12. 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.

13. Thank You! Professor Kryn Stankunas Brynn Simek Stankunas Lab – Fern Bosada – Vidusha Devasthali – Ben Smood – Alex Akerberg – Cho Li – Alan Gomez – Scott Stewart