Fig 9. Schematic representation of the Pitx2>Wnt>ROS signaling pathway in NppaCrePitx2-/- insufficiency mice, as compared to experimental HTD and HTN (SHR) rat models.

Observe that Pitx2 insufficiency leads deregulation of Zfhx3 and Wnt signaling, which subsequently leads to microRNA and ROS signaling deregulation and thus ion channel impairment. In HTD but not in HTN, Pitx2>Wnt>ROS signaling is also impaired. Furthermore, in vitro gain- and loss-of-function analyses (brown arrows) further support a complex retroactive gene regulatory network.