On the other hand, many Notch pathway genes are regulated by HIF (41, 59, 60) and hence, the stabilization of HIF caused by deletion of Hif-p4h-2 may interfere Notch signaling via modifying the expression of, for example, Notch3, Dll1, Dll4, Jag2, and Hes1. The imbalance between HIF and Notch pathways is likely to play a crucial role in cyst formation and the failure in regeneration of HFs in the cKO skin. Here, HES1 is linked to Hand-foot syndrome.