Fig. 8.

A Shox2–Nkx2-5 antagonism seesaw model links the pacemaker program in the PV myocardium to the SAN. A seesaw model explains the genetic ‘weight shift’ between Shox2 and Nkx2-5 to determine cell fate in the venous pole derivatives. In this model it is proposed that, at the early developmental stage, Shox2 is expressed ‘heavily’ in the venous pole derivatives including the SAN, PV and CS that exhibit pacemaker charateristics. As the venous pole develops and becomes mature, the ‘weight’ of Nkx2-5 activity increases, enabling the venous pole derivatives, except the SAN, to adopt an atrial-like working myocardial fate gradually.