PUBLICATION

Genome-wide analysis of facial skeletal regionalization in zebrafish

Authors

Askary, A., Xu, P., Barske, L., Bay, M., Bump, P., Balczerski, B., Bonaguidi, M.A., Crump, J.G.

ID

ZDB-PUB-170715-7

Date

2017

Source

Development (Cambridge, England) 144(16): 2994-3005 (Journal)

Registered Authors

Balczerski, Bartosz, Barske, Lindsey, Crump, Gage DeKoeyer, Xu, Peng-Fei

Keywords

Bone, Cartilage, Cranial neural crest, Craniofacial, Dlx5a, Dorsoventral patterning, Edn1, Emx2, Endothelin, Fsta, Hand2, Jagged-Notch, Jaw, Mrrf, Skeleton, Zebrafish

Datasets

GEO:GSE95812

MeSH Terms

Zebrafish/embryology*
Zebrafish/genetics*
In Situ Hybridization
Body Patterning/genetics
Body Patterning/physiology
Gene Expression Regulation, Developmental/genetics
Gene Expression Regulation, Developmental/physiology
Flow Cytometry
Animals
Endothelin-1/genetics
Endothelin-1/metabolism
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Branchial Region/embryology
Branchial Region/metabolism

(all 15)

PubMed

28705894 Full text @ Development

Abstract

Patterning of the facial skeleton involves the precise deployment of thousands of genes in distinct regions of the pharyngeal arches. Despite the significance for craniofacial development, how genetic programs drive this regionalization remains incompletely understood. Here we use combinatorial labeling of zebrafish cranial neural crest-derived cells (CNCCs) to define global gene expression along the dorsoventral axis of the developing arches. Intersection of region-specific transcriptomes with expression changes in response to signaling perturbations demonstrates complex roles for Endothelin 1 (Edn1) signaling in the intermediate joint-forming region, yet a surprisingly minor role in ventralmost regions. Analysis of co-variance across multiple sequencing experiments further reveals clusters of co-regulated genes, with in situ hybridization confirming the domain-specific expression of novel genes. We then created loss-of-function alleles for 12 genes and uncovered antagonistic functions of two new Edn1 targets, follistatin a (fsta) and emx2, in regulating cartilaginous joints in the hyoid arch. Our unbiased discovery and functional analysis of genes with regional expression in zebrafish arch CNCCs reveals complex regulation by Edn1 and points to novel candidates for craniofacial disorders.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
ccn2b	edn1^{tf216b/tf216b}; el10Tg; y1Tg	standard conditions	Prim-25	pharyngeal arch 1 medial region	ISH	Fig. 4
ccn2b	edn1^{tf216b/tf216b}; el10Tg; y1Tg	standard conditions	Prim-25	pharyngeal arch 2 medial region	ISH	Fig. 4
ccn2b	el10Tg; y1Tg	standard conditions	Prim-25	pharyngeal arch 1 medial region	ISH	Fig. 4
ccn2b	el10Tg; y1Tg	standard conditions	Prim-25	pharyngeal arch 2 medial region	ISH	Fig. 4
ccn2b	el375Tg	standard conditions	Prim-25	pharyngeal arch 1 medial region	ISH	Fig. 2
ccn2b	el375Tg	standard conditions	Prim-25	pharyngeal arch 2 medial region	ISH	Fig. 2
cd248a	edn1^{tf216b/tf216b}; el10Tg; y1Tg	standard conditions	Prim-25	pharyngeal arch 1 dorsal region	ISH	Fig. 4
cd248a	edn1^{tf216b/tf216b}; el10Tg; y1Tg	standard conditions	Prim-25	pharyngeal arch 2 dorsal region	ISH	Fig. 4
cd248a	el10Tg; y1Tg	standard conditions	Prim-25	pharyngeal arch 1 dorsal region	ISH	Fig. 4
cd248a	el10Tg; y1Tg	standard conditions	Prim-25	pharyngeal arch 2 dorsal region	ISH	Fig. 4

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
ccn2a^el654/el654	standard conditions	Day 5	cranium morphology, normal	text only
ccn2b^el689/el689	standard conditions	Day 5	cranium morphology, normal	text only
cd248a^el679/el679	standard conditions	Day 5	cranium morphology, normal	text only
cdh11^el520/el520	standard conditions	Day 5	cranium morphology, normal	text only
edn1^{tf216b/tf216b}	standard conditions	Day 5	opercle increased variability of size, abnormal	Fig. S4
edn1^{tf216b/tf216b}; el10Tg; y1Tg	standard conditions	Prim-25	pharyngeal arch 1 medial region ccn2b expression decreased amount, abnormal	Fig. 4
edn1^{tf216b/tf216b}; el10Tg; y1Tg	standard conditions	Prim-25	pharyngeal arch 1 medial region cdh11 expression spatial pattern, abnormal	Fig. 4
edn1^{tf216b/tf216b}; el10Tg; y1Tg	standard conditions	Prim-25	pharyngeal arch 1 medial region fsta expression decreased amount, abnormal	Fig. 4
edn1^{tf216b/tf216b}; el10Tg; y1Tg	standard conditions	Prim-25	pharyngeal arch 1 medial region pou3f3a expression increased distribution, abnormal	Fig. 4
edn1^{tf216b/tf216b}; el10Tg; y1Tg	standard conditions	Prim-25	pharyngeal arch 1 medial region pou3f3b expression increased distribution, abnormal	Fig. 4

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
b1105		Point Mutation	jag1b
el10Tg	Tg(sox10:DsRed)	Transgenic Insertion
el375Tg	Tg(sox10:EGFP-CAAX)	Transgenic Insertion
el520		Small Deletion	cdh11
el538		Indel	irx7
el574		Small Deletion	irx5a
el586		Small Deletion	emx2
el593		Small Deletion	osr1
el595		Small Deletion	osr2
el624		Small Deletion	fsta

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
cd248a	CRISPR1-cd248a	CRISPR
cdh11	TALEN1-cdh11	TALEN
ccn2a	CRISPR7-ccn2a	CRISPR
ccn2b	CRISPR1-ccn2b	CRISPR
emx2	TALEN1-emx2	TALEN
fsta	CRISPR1-fsta	CRISPR
fstb	CRISPR1-fstb	CRISPR
her6	TALEN1-her6	TALEN
mrrf	CRISPR1-mrrf	CRISPR
osr1	TALEN1-osr1	TALEN

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Fish

Fish
ccn2a^el654/el654
ccn2b^el689/el689
cd248a^el679/el679
cdh11^el520/el520
dlx5a^j1073aGt; el10Tg
edn1^{tf216b/tf216b}
edn1^{tf216b/tf216b}; el10Tg; y1Tg
edn1^{tf216b/tf216b}; emx2^el586/el586
el10Tg; pd24Tg
el10Tg; y1Tg

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Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
DsRed	EFG	DsRed
EGFP	EFG	EGFP

Mapping

Askary et al., 2017 ZDB-PUB-170715-7 PMID:28705894

Genome-wide analysis of facial skeletal regionalization in zebrafish

Askary et al., 2017

ZDB-PUB-170715-7
PMID:28705894