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Nkx2.5 regulates endothelin converting enzyme‐1 during pharyngeal arch patterning
Author(s) -
Iklé Jennifer M.,
Tavares Andre L. P.,
King Marisol,
Ding Hailei,
Colombo Sophie,
Firulli Beth A.,
Firulli Anthony B.,
Targoff Kimara L.,
Yelon Deborah,
Clouthier David E.
Publication year - 2017
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.23021
Subject(s) - zebrafish , biology , neural crest , microbiology and biotechnology , morpholino , endothelin 1 , phenotype , branchial arch , anatomy , receptor , gene , genetics , embryo
In gnathostomes, dorsoventral (D‐V) patterning of neural crest cells (NCC) within the pharyngeal arches is crucial for the development of hinged jaws. One of the key signals that mediate this process is Endothelin‐1 (EDN1). Loss of EDN1 binding to the Endothelin‐A receptor (EDNRA) results in loss of EDNRA signaling and subsequent facial birth defects in humans, mice and zebrafish. A rate‐limiting step in this crucial signaling pathway is the conversion of immature EDN1 into a mature active form by Endothelin converting enzyme‐1 (ECE1). However, surprisingly little is known about how Ece1 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 ece1 expression. Disruption of nkx2.5 in zebrafish embryos results in defects in both ventral and dorsal pharyngeal arch‐derived elements, with changes in ventral arch gene expression consistent with a disruption in Ednra signaling. ece1 mRNA rescues the nkx2.5 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.