PUBLICATION

Zebrafish eda and edar mutants reveal conserved and ancestral roles of ectodysplasin signaling in vertebrates

Authors

Harris, M.P., Rohner, N., Schwarz, H., Perathoner, S., Konstantinidis, P., and Nüsslein-Volhard, C.

ID

ZDB-PUB-081008-12

Date

2008

Source

PLoS Genetics 4(10): e1000206 (Journal)

Registered Authors

Harris, Matthew, Nüsslein-Volhard, Christiane, Rohner, Nicolas

Keywords

Zebrafish, Developmental signaling, Alleles, Epidermis, Teeth, Phenotypes, Skull, Adults

MeSH Terms

Ectodysplasins/genetics
Ectodysplasins/metabolism*
Animals
Signal Transduction*
Body Patterning
Zebrafish/genetics
Zebrafish/growth & development*
Zebrafish/metabolism
Skeleton
Edar Receptor/genetics
Edar Receptor/metabolism*
Humans
Mutation*
Evolution, Molecular*
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Vertebrates/genetics
Vertebrates/growth & development
Vertebrates/metabolism
Epidermis/growth & development
Epidermis/metabolism
Ectodermal Dysplasia/genetics
Ectodermal Dysplasia/metabolism*

(all 23)

PubMed

18833299 Full text @ PLoS Genet.

Abstract

The genetic basis of the development and variation of adult form of vertebrates is not well understood. To address this problem, we performed a mutant screen to identify genes essential for the formation of adult skeletal structures of the zebrafish. Here, we describe the phenotypic and molecular characterization of a set of mutants showing loss of adult structures of the dermal skeleton, such as the rays of the fins and the scales, as well as the pharyngeal teeth. The mutations represent adult-viable, loss of function alleles in the ectodysplasin (eda) and ectodysplasin receptor (edar) genes. These genes are frequently mutated in the human hereditary disease hypohidrotic ectodermal dysplasia (HED; OMIM 224900, 305100) that affects the development of integumentary appendages such as hair and teeth. We find mutations in zebrafish edar that affect similar residues as mutated in human cases of HED and show similar phenotypic consequences. eda and edar are not required for early zebrafish development, but are rather specific for the development of adult skeletal and dental structures. We find that the defects of the fins and scales are due to the role of Eda signaling in organizing epidermal cells into discrete signaling centers of the scale epidermal placode and fin fold. Our genetic analysis demonstrates dose-sensitive and organ-specific response to alteration in levels of Eda signaling. In addition, we show substantial buffering of the effect of loss of edar function in different genetic backgrounds, suggesting canalization of this developmental system. We uncover a previously unknown role of Eda signaling in teleosts and show conservation of the developmental mechanisms involved in the formation and variation of both integumentary appendages and limbs. Lastly, our findings point to the utility of adult genetic screens in the zebrafish in identifying essential developmental processes involved in human disease and in morphological evolution.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
bmp2b	edar^{te370f/te370f} (TU)	standard conditions	Days 21-29	Not Detected	epidermis	ISH	Fig. 1
bmp2b	edar^{te370f/te370f} (TU)	standard conditions	Days 21-29		pectoral fin lepidotrichium	ISH	Fig. 7
bmp2b	edar^{te370f/te370f} (TU)	standard conditions	Days 21-29		pelvic fin lepidotrichium	ISH	Fig. 7
bmp2b	WT	standard conditions	Days 21-29		caudal fin lepidotrichium	ISH	Fig. 8
bmp2b	WT	standard conditions	Days 21-29		epidermis	ISH	Fig. 4
bmp2b	WT	standard conditions	Days 21-29		pectoral fin lepidotrichium	ISH	Fig. 7
bmp2b	WT	standard conditions	Days 21-29		pelvic fin lepidotrichium	ISH	Fig. 7
eda	WT	standard conditions	Days 21-29		epidermis	ISH	Fig. 4
eda	WT	standard conditions	Days 30-44		scale	ISH	Fig. 4
edar	edar^{te370f/te370f} (TU)	standard conditions	Days 21-29		pectoral fin lepidotrichium	ISH	Fig. 7

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
eda^dt1261/+ (TL)	standard conditions	Adult	ceratobranchial 5 tooth decreased amount, abnormal	Fig. 2
eda^dt1261/+ (TL)	standard conditions	Adult	gill raker decreased size, abnormal	Fig. 2
eda^dt1261/+ (TL)	standard conditions	Adult	lepidotrichium morphology, normal	Fig. 2
eda^dt1261/+ (TL)	standard conditions	Adult	scale decreased amount, abnormal	Fig. 2
eda^dt1261/+ (TL)	standard conditions	Adult	whole organism size, normal	Fig. 2
eda^dt1261/+ (TL)	standard conditions	Adult	whole organism viable, normal	Fig. 2
eda^{dt1261/dt1261} (TL)	standard conditions	Adult	anal fin distal radial spatial pattern, normal	Fig. 6
eda^{dt1261/dt1261} (TL)	standard conditions	Adult	anal fin lepidotrichium aplastic, abnormal	Fig. 6
eda^{dt1261/dt1261} (TL)	standard conditions	Adult	anal fin proximal radial spatial pattern, normal	Fig. 6
eda^{dt1261/dt1261} (TL)	standard conditions	Adult	caudal fin lepidotrichium aplastic, abnormal	Fig. 6

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Mutations / Transgenics

Allele	Type	Affected Genomic Region
dt1248	Point Mutation	edar
dt1261	Point Mutation	eda
t0621	Point Mutation	edar
te370f	Unknown	edar

Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
edar^{dt1248/dt1248} (TL)
edar^dt1248/+ (TL)
edar^t0621/+; edar^te370f/+
edar^t0621/t0621 (TL)
edar^{te370f/te370f} (TU)
eda^{dt1261/dt1261} (TL)
eda^dt1261/+ (TL)
WT

Antibodies

Orthology

Gene	Orthology
eda
edar

Engineered Foreign Genes

Mapping

Entity Type	Entity Symbol	Location
Feature	dt1261	Chr: 5 Details
Feature	te370f	Chr: 9 Details
GENE	eda	Chr: 5 Details
GENE	edar	Chr: 9 Details
SSLP	z1566	Chr: 9 Details
SSLP	z10484	Chr: 5 Details
SSLP	z13866	Chr: 5 Details
SSLP	z20031	Chr: 9 Details

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Harris et al., 2008 ZDB-PUB-081008-12 PMID:18833299

Zebrafish eda and edar mutants reveal conserved and ancestral roles of ectodysplasin signaling in vertebrates

Harris et al., 2008

ZDB-PUB-081008-12
PMID:18833299