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One of the key signals that mediate this process is Endothelin\u20101 (EDN1). Loss of EDN1 binding to the Endothelin\u2010A receptor (EDNRA) results in loss of EDNRA signaling and subsequent facial birth defects in humans, mice and zebrafish. A rate\u2010limiting step in this crucial signaling pathway is the conversion of immature EDN1 into a mature active form by Endothelin converting enzyme\u20101 (ECE1). However, surprisingly little is known about how <jats:italic>Ece1<\/jats:italic> transcription is induced or regulated. We show here that Nkx2.5 is required for proper craniofacial development in zebrafish and acts in part by upregulating <jats:italic>ece1<\/jats:italic> expression. Disruption of <jats:italic>nkx2.5<\/jats:italic> in zebrafish embryos results in defects in both ventral and dorsal pharyngeal arch\u2010derived elements, with changes in ventral arch gene expression consistent with a disruption in Ednra signaling. <jats:italic>ece1<\/jats:italic> mRNA rescues the <jats:italic>nkx2.5<\/jats:italic> morphant phenotype, indicating that Nkx2.5 functions through modulating Ece1 expression or function. These studies illustrate a new function for Nkx2.5 in embryonic development and provide new avenues with which to pursue potential mechanisms underlying human facial disorders.<\/jats:p>","DOI":"10.1002\/dvg.23021","type":"journal-article","created":{"date-parts":[[2017,1,21]],"date-time":"2017-01-21T01:42:38Z","timestamp":1484962958000},"source":"Crossref","is-referenced-by-count":11,"title":["Nkx2.5 regulates endothelin converting enzyme\u20101 during pharyngeal arch patterning"],"prefix":"10.1002","volume":"55","author":[{"given":"Jennifer M.","family":"Ikl\u00e9","sequence":"first","affiliation":[{"name":"Department of Craniofacial Biology University of Colorado Anschutz Medical Campus Aurora Colorado 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre L. 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