PUBLICATION

RA and FGF Signalling Are Required in the Zebrafish Otic Vesicle to Pattern and Maintain Ventral Otic Identities

Authors

Maier, E.C., Whitfield, T.T.

ID

ZDB-PUB-141205-2

Date

2014

Source

PLoS Genetics 10: e1004858 (Journal)

Registered Authors

Maier, Esther, Whitfield, Tanya T.

Keywords

Embryos, Developmental signaling, Zebrafish, Signal inhibition, Neuroblasts, Ears, Vesicles, Epithelium

MeSH Terms

Fibroblast Growth Factors/pharmacology*
Organisms, Genetically Modified
Signal Transduction/drug effects
Signal Transduction/genetics
Body Patterning*/drug effects
Body Patterning*/genetics
Animals
Gene Expression Regulation, Developmental/drug effects
Ear, Inner/drug effects*
Ear, Inner/embryology*
Ear, Inner/metabolism
Tretinoin/pharmacology*
Zebrafish*/embryology
Zebrafish*/genetics
Embryo, Nonmammalian

(all 15)

PubMed

25473832 Full text @ PLoS Genet.

Abstract

During development of the zebrafish inner ear, regional patterning in the ventral half of the otic vesicle establishes zones of gene expression that correspond to neurogenic, sensory and non-neural cell fates. FGF and Retinoic acid (RA) signalling from surrounding tissues are known to have an early role in otic placode induction and otic axial patterning, but how external signalling cues are translated into intrinsic patterning during otic vesicle (OV) stages is not yet understood. FGF and RA signalling pathway members are expressed in and around the OV, suggesting important roles in later patterning or maintenance events. We have analysed the temporal requirement of FGF and RA signalling for otic development at stages after initial anteroposterior patterning has occurred. We show that high level FGF signalling acts to restrict sensory fates, whereas low levels favour sensory hair cell development; in addition, FGF is both required and sufficient to promote the expression of the non-neural marker otx1b in the OV. RA signalling has opposite roles: it promotes sensory fates, and restricts otx1b expression and the development of non-neural fates. This is surprisingly different from the earlier requirement for RA signalling in specification of non-neural fates via tbx1 expression, and highlights the shift in regulation that takes place between otic placode and vesicle stages in zebrafish. Both FGF and RA signalling are required for the development of the otic neurogenic domain and the generation of otic neuroblasts. In addition, our results indicate that FGF and RA signalling act in a feedback loop in the anterior OV, crucial for pattern refinement.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
aldh1a2	AB	standard conditions	Prim-5		mesenchyme	ISH	Fig. 1
aldh1a2	AB	standard conditions	14-19 somites		mesenchyme	ISH	Fig. 1
aldh1a2	AB	standard conditions	20-25 somites		mesenchyme	ISH	Fig. 1
aldh1a3	AB	standard conditions	20-25 somites		otic vesicle antero-ventral region	ISH	Fig. 1
aldh1a3	AB	standard conditions	Prim-5		otic vesicle antero-ventral region	ISH	Fig. 1
aldh1a3	AB	chemical treatment: SU5402	Prim-5	Not Detected	otic vesicle	ISH	Fig. 9
aldh1a3	AB	control	Prim-5		otic vesicle	ISH	Fig. 9
aldh1a3	fgf3^{t21142/t21142}	standard conditions	Prim-5	Not Detected	otic vesicle	ISH	Fig. 9
aldh1a3	fgf8a^{ti282a/ti282a}	standard conditions	Prim-5	Not Detected	otic vesicle	ISH	Fig. 9
aldh1a3	WT	standard conditions	Prim-5		otic vesicle	ISH	Fig. 9

1 - 10 of 197

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB	chemical treatment: 4-(diethylamino)benzaldehyde	Prim-5	otic vesicle decreased size, abnormal	Fig. 7
WT	chemical treatment: 4-(diethylamino)benzaldehyde	Prim-5	otic vesicle decreased size, abnormal	Fig. 7
fgf3^{t21142/t21142}	standard conditions	Prim-5	macula adjacent to macula, abnormal	Fig. 3
fgf3^{t21142/t21142}	standard conditions	Prim-5	macula fused with macula, abnormal	Fig. 3
fgf3^{t21142/t21142}	standard conditions	Long-pec	posterior macula has extra parts of type hair cell, abnormal	Fig. 3
fgf3^{t21142/t21142}	standard conditions	Long-pec	posterior macula increased size, abnormal	Fig. 3
fgf8a^{ti282a/ti282a}	standard conditions	Prim-5	otic vesicle decreased size, abnormal	Fig. 3
fgf8a^{ti282a/ti282a}	standard conditions	Long-pec	posterior macula decreased size, abnormal	Fig. 3
fgf8a^{ti282a/ti282a}	standard conditions	Long-pec	posterior macula has fewer parts of type hair cell, abnormal	Fig. 3
otx1^sa96/sa96	chemical treatment: 4-(diethylamino)benzaldehyde	Prim-5	otic vesicle decreased size, abnormal	Fig. 7

1 - 10 of 17

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
i26		Point Mutation	aldh1a2
pd18Tg	Tg(hsp70l:dnraraa-EGFP)	Transgenic Insertion
s356tTg	Tg(pou4f3:GAP-GFP)	Transgenic Insertion
sa96		Point Mutation	otx1
t21142		Point Mutation	fgf3
ti282a		Point Mutation	fgf8a
tm208		Point Mutation	tbx1
w2		Point Mutation	mitfa
zf115Tg	Tg(hsp70l:fgf3-MYC)	Transgenic Insertion

1 - 9 of 9

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
aldh1a3	MO1-aldh1a3	MRPHLNO

Fish

Fish
AB
AB + MO1-aldh1a3
aldh1a2^i26/i26
fgf3^{t21142/t21142}
fgf8a^{ti282a/ti282a}
mitfa^w2/w2
otx1^sa96/sa96
pd18Tg
s356tTg
s356tTg; zf115Tg

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GFP	EFG	GFP

Mapping

Maier et al., 2014 ZDB-PUB-141205-2 PMID:25473832

RA and FGF Signalling Are Required in the Zebrafish Otic Vesicle to Pattern and Maintain Ventral Otic Identities

Maier et al., 2014

ZDB-PUB-141205-2
PMID:25473832