Mechanisms Of Nkx2-5 Dependent Left-Right Asymmetry Of The Cardiac Crescent

Previous studies have defined a role for Nodal, Cripto and Pitx2c in left-right (LR) asymmetry. The transcriptional patterning of the cardiac crescent has not been previously described. We have engineered and utilized a 6 kb Nkx2–5-EYFP transgenic mouse that directs reporter expression in cardiac progenitors and combinatorially mated them into the wildtype (WT) or Nkx2–5 mutant backgrounds. Staged embryos were bisected, cardiac progenitors were collected using FACS and the signature of gene expression of cardiac progenitors that populate the left vs. the right regions of the cardiac crescent were examined. We observed that the left side of the WT cardiac crescent had increased expression of Nodal, Cripto and Pitx2 transcripts that are known to have functions critical to future chamber myocardium as well as Nkx2–5. The right side of the crescent was not enriched for a specific gene program however enrichment was noted for Hoxa9 and Hoxa10. We analyzed the same LR transcriptional program in the Nkx2–5 mutan...