PUBLICATION

Nkx2.5 regulates Endothelin Converting Enzyme-1 during pharyngeal arch patterning

Authors

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.

ID

ZDB-PUB-170122-1

Date

2017

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

MeSH Terms

Endothelin-Converting Enzymes/genetics*
Endothelin-Converting Enzymes/metabolism
Pharynx/embryology
Pharynx/metabolism
Zebrafish
Gene Expression Regulation, Developmental*
Mice
Animals
Up-Regulation
Zebrafish Proteins/genetics*
Zebrafish Proteins/metabolism
Neural Crest/embryology
Neural Crest/metabolism*
Homeobox Protein Nkx-2.5/genetics*
Homeobox Protein Nkx-2.5/metabolism

PubMed

28109039 Full text @ Genesis

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 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.

Genes / Markers

Figures

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Expression

Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
WT	standard conditions	Prim-5		pharyngeal arch	ISH	Fig. 6
WT	standard conditions	Prim-5		whole organism	RTPCR	Fig. 6
WT + MO2-nkx2.5	standard conditions	Prim-5		pharyngeal arch	ISH	Fig. 6
WT + MO2-nkx2.5	standard conditions	Prim-5		whole organism	RTPCR	Fig. 6
WT	standard conditions	Prim-5		pharyngeal arch 1	ISH	Fig. 6
WT	standard conditions	Prim-5		pharyngeal arch 2	ISH	Fig. 6
WT	standard conditions	Prim-5		whole organism	RTPCR	Fig. 6
WT + MO2-nkx2.5	standard conditions	Prim-5	Not Detected	pharyngeal arch 1	ISH	Fig. 6
WT + MO2-nkx2.5	standard conditions	Prim-5	Not Detected	pharyngeal arch 2	ISH	Fig. 6
WT + MO2-nkx2.5	standard conditions	Prim-5		whole organism	RTPCR	Fig. 6

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-ece1 + MO4-tp53	standard conditions	Prim-5	pharyngeal arch 1 dlx5a expression decreased distribution, abnormal	Fig. 2
WT + MO1-ece1 + MO4-tp53	standard conditions	Prim-5	pharyngeal arch 2 dlx5a expression decreased distribution, abnormal	Fig. 2
WT + MO1-ece1 + MO4-tp53	standard conditions	Day 5	basihyal cartilage curved ventral, abnormal	Fig. 2
WT + MO1-ece1 + MO4-tp53	standard conditions	Day 5	basihyal cartilage decreased size, abnormal	Fig. 2
WT + MO1-ece1 + MO4-tp53	standard conditions	Day 5	ceratobranchial cartilage decreased amount, abnormal	Fig. 2
WT + MO1-ece1 + MO4-tp53	standard conditions	Day 5	ceratohyal cartilage curved ventral, abnormal	Fig. 2
WT + MO1-ece1 + MO4-tp53	standard conditions	Day 5	ceratohyal cartilage decreased size, abnormal	Fig. 2
WT + MO1-ece1 + MO4-tp53	standard conditions	Day 5	ceratohyal cartilage fused with hyosymplectic cartilage, abnormal	Fig. 2
WT + MO1-ece1 + MO4-tp53	standard conditions	Day 5	hyosymplectic cartilage hypoplastic, abnormal	Fig. 2
WT + MO1-ece1 + MO4-tp53	standard conditions	Day 5	Meckel's cartilage curved ventral, abnormal	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
co10Tg	Tg(hand2:mCherry,myl7:EGFP)	Transgenic Insertion
vu179		Point Mutation	nkx2.5

Human Disease / Model

Sequence Targeting Reagents

Fish

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
mCherry	EFG	mCherry

Mapping

Iklé et al., 2017 ZDB-PUB-170122-1 PMID:28109039

Nkx2.5 regulates Endothelin Converting Enzyme-1 during pharyngeal arch patterning

Iklé et al., 2017

ZDB-PUB-170122-1
PMID:28109039