Sox9-and scleraxis-cre lineage fate mapping in aortic and mitral valve structures

Abstract

Heart valves are complex structures composed of a heterogeneous population of valve interstitial cells (VICs), an overlying endothelium and highly organized layers of extracellular matrix. Alterations in valve homeostasis are characteristic of dysfunction and disease, however the mechanisms that initiate and promote valve pathology are poorly understood. Advancements have been largely hindered by the limited availability of tools for gene targeting in heart valve structures during embryogenesis and after birth. We have previously shown that the transcription factors Sox9 and Scleraxis (Scx) are required for heart valve formation and in this study we describe the recombination patterns of Sox9-and Scx-Cre lines at differential time points in aortic and mitral valve structures. In ScxCre; ROSA26GFP mice, recombination is undetected in valve endothelial cells (VECs) and low in VICs during embryogenesis. However, recombination increases in VICs from post natal stages and by 4 weeks side-specific patterns are observed. Using the inducible Sox9CreERT2 system, we observe recombination in VECs and VICs in the embryo, and high levels are maintained through post natal and juvenile stages. These Cre-drivers provide the field with new tools for gene targeting in valve cell lineages during differential stages of embryonic and post natal maturation and maintenance.