Endothelin signaling activates Mef2c expression in the neural crest through a MEF2C-dependent positive-feedback transcriptional pathway

Jianxin Hu, Michael P. Verzi, Ashley S. Robinson, Paul Ling Fung Tang, Lisa L. Hua, Shan Mei Xu, Pui Yan Kwok, Brian L. Black

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Endothelin signaling is essential for neural crest development, and dysregulated Endothelin signaling is associated with several neural crest-related disorders, including Waardenburg and other syndromes. However, despite the crucial roles of this pathway in neural crest development and disease, the transcriptional effectors directly activated by Endothelin signaling during neural crest development remain incompletely elucidated. Here, we establish that the MADS box transcription factor MEF2C is an immediate downstream transcriptional target and effector of Endothelin signaling in the neural crest. We show that Endothelin signaling activates Mef2c expression in the neural crest through a conserved enhancer in the Mef2c locus and that CRISPR-mediated deletion of this Mef2c neural crest enhancer from the mouse genome abolishes Endothelin induction of Mef2c expression. Moreover, we demonstrate that Endothelin signaling activates neural crest expression of Mef2c by de-repressing MEF2C activity through a Calmodulin-CamKII-histone deacetylase signaling cascade. Thus, these findings identify a MEF2C-dependent, positive-feedback mechanism for Endothelin induction and establish MEF2C as an immediate transcriptional effector and target of Endothelin signaling in the neural crest.

Original languageEnglish (US)
Pages (from-to)2775-2780
Number of pages6
JournalDevelopment (Cambridge)
Volume142
Issue number16
DOIs
StatePublished - Aug 15 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

Keywords

  • Craniofacial development
  • Endothelin
  • MEF2C
  • Melanocytes
  • Mouse
  • Neural crest
  • Transcription

Fingerprint Dive into the research topics of 'Endothelin signaling activates Mef2c expression in the neural crest through a MEF2C-dependent positive-feedback transcriptional pathway'. Together they form a unique fingerprint.

Cite this