Nkx2.5 regulates endothelin converting enzyme-1 during pharyngeal arch patterning

Jennifer M. Iklé, Andre L P Tavares, Marisol King, Hailei Ding, Sophie Colombo, Beth A. Firulli, Anthony Firulli, Kimara L. Targoff, Deborah Yelon, David E. Clouthier

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalGenesis
DOIs
StateAccepted/In press - 2017

Fingerprint

Branchial Region
Endothelin-1
Zebrafish
Endothelin A Receptors
Neural Crest
Jaw
Embryonic Development
Embryonic Structures
Phenotype
Gene Expression
Messenger RNA
Endothelin-Converting Enzymes

Keywords

  • Birth defects
  • Neural crest
  • Patterning
  • Signaling
  • Transcription

ASJC Scopus subject areas

  • Genetics
  • Endocrinology
  • Cell Biology

Cite this

Iklé, J. M., Tavares, A. L. P., King, M., Ding, H., Colombo, S., Firulli, B. A., ... Clouthier, D. E. (Accepted/In press). Nkx2.5 regulates endothelin converting enzyme-1 during pharyngeal arch patterning. Genesis. https://doi.org/10.1002/dvg.23021

Nkx2.5 regulates endothelin converting enzyme-1 during pharyngeal arch patterning. / Iklé, Jennifer M.; Tavares, Andre L P; King, Marisol; Ding, Hailei; Colombo, Sophie; Firulli, Beth A.; Firulli, Anthony; Targoff, Kimara L.; Yelon, Deborah; Clouthier, David E.

In: Genesis, 2017.

Research output: Contribution to journalArticle

Iklé, JM, Tavares, ALP, King, M, Ding, H, Colombo, S, Firulli, BA, Firulli, A, Targoff, KL, Yelon, D & Clouthier, DE 2017, 'Nkx2.5 regulates endothelin converting enzyme-1 during pharyngeal arch patterning', Genesis. https://doi.org/10.1002/dvg.23021
Iklé, Jennifer M. ; Tavares, Andre L P ; King, Marisol ; Ding, Hailei ; Colombo, Sophie ; Firulli, Beth A. ; Firulli, Anthony ; Targoff, Kimara L. ; Yelon, Deborah ; Clouthier, David E. / Nkx2.5 regulates endothelin converting enzyme-1 during pharyngeal arch patterning. In: Genesis. 2017.
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