Endothelin 1/endothelin type A receptor signaling pathway are regulated by non-coding RNAs and epigenetic alternation in pharyngeal arch development.

内皮素-1通过内皮素-1/A受体→Dlx5/6→Hand2信号通路决定下颌骨的特性。在颧弓中，Dlx5/6和EVF2的表达依赖于ET-1。Dlx5/6是Dlx5/6基因座上的一个非编码RNA，负向调节Dlx5/6的表达。另一方面，mI56I Dlx5/6区域的增强子活性受Dlx5/6自身的正调控。这些结果表明，ET-1/ETAR信号至少部分通过mI56增强子和EVF2的正/负反馈环诱导Dlx5/6的表达。

Endothelin-1 determines mandibular identity though endothelin-1/endothelin receptor type-A → Dlx5/6 → Hand2 signaling pathway. In the branchial arches, the expression of Dlx5/6 and Evf2, a non-coding RNA in the Dlx5/6 locus where negatively regulates Dlx5/6 expression, depends on ET-1. On the other hand, the enhancer activity of the mI56i Dlx5/6 region is positively regulated by Dlx5/6 themselves. These results indicate that the ET-1/ETAR signal induces Dlx5/6 expression at least partly through positive/negative feedback loop via mI56 enhancer and Evf2.