Upstream of CCF formation, regulation of mitochondrial ROS, and downstream signaling pathways are beginning to emerge as important targets: the HDACi trichostatin A and SAHA prevent CCF formation by reducing mtROS through an indirect mechanism (also in vivo), and the JNKi SP600125 prevents CCF formation by blocking JNK1/2 activation downstream of mitochondrial ROS (Vizioli et al., 2020). This evidence concerns the gene MAPK8 and clubfoot.