|ZFIN ID: ZDB-PUB-170122-1|
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Nkx2.5 regulates Endothelin Converting Enzyme-1 during pharyngeal arch patterning
Iklé, J.M., Tavares, A.L., King, M., Ding, H., Colombo, S., Firulli, B.A., Fiulli, A.B., Targoff, K.L., Yelon, D., Clouthier, D.E.
|Source:||Genesis (New York, N.Y. : 2000) 55(3): (Journal)|
|Registered Authors:||Clouthier, David, Colombo, Sophie, Ding, Hailei, Targoff, Kimara, Yelon, Deborah|
|Keywords:||Birth defects, Neural crest, Patterning, Signaling, Transcription|
|PubMed:||28109039 Full text @ Genesis|
Iklé, J.M., Tavares, A.L., King, M., Ding, H., Colombo, S., Firulli, B.A., Fiulli, A.B., Targoff, K.L., Yelon, D., Clouthier, D.E. (2017) Nkx2.5 regulates Endothelin Converting Enzyme-1 during pharyngeal arch patterning. Genesis (New York, N.Y. : 2000). 55(3).
ABSTRACTIn 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 mediates 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. This article is protected by copyright. All rights reserved.