PUBLICATION

Anteroposterior patterning of the zebrafish ear through Fgf- and Hh-dependent regulation of hmx3a expression

Authors

Hartwell, R.D., England, S.J., Monk, N.A.M., van Hateren, N.J., Baxendale, S., Marzo, M., Lewis, K.E., Whitfield, T.T.

ID

ZDB-PUB-190426-5

Date

2019

Source

PLoS Genetics 15: e1008051 (Journal)

Registered Authors

Baxendale, Sarah, England, Sam, Hartwell, Ryan, Lewis, Katharine E., Van Hateren, Nicholas J., Whitfield, Tanya T.

Keywords

none

MeSH Terms

Transcription Factors/genetics*
Body Patterning/genetics*
Hedgehog Proteins/metabolism*
Gene Expression Regulation, Developmental
Animals
Ear/embryology*
Phenotype
Fibroblast Growth Factors/metabolism*
Zebrafish Proteins/genetics*
Signal Transduction
Embryo, Nonmammalian
Zebrafish/embryology*
Zebrafish/physiology*

(all 13)

PubMed

31022185 Full text @ PLoS Genet.

Abstract

In the zebrafish, Fgf and Hh signalling assign anterior and posterior identity, respectively, to the poles of the developing ear. Mis-expression of fgf3 or inhibition of Hh signalling results in double-anterior ears, including ectopic expression of hmx3a. To understand how this double-anterior pattern is established, we characterised transcriptional responses in Fgf gain-of-signalling or Hh loss-of-signalling backgrounds. Mis-expression of fgf3 resulted in rapid expansion of anterior otic markers, refining over time to give the duplicated pattern. Response to Hh inhibition was very different: initial anteroposterior asymmetry was retained, with de novo duplicate expression domains appearing later. We show that Hmx3a is required for normal anterior otic patterning, and that otic patterning defects in hmx3a-/- mutants are a close phenocopy to those seen in fgf3-/- mutants. However, neither loss nor gain of hmx3a function was sufficient to generate full ear duplications. Using our data to infer a transcriptional regulatory network required for acquisition of otic anterior identity, we can recapitulate both the wild-type and the double-anterior pattern in a mathematical model.

Genes / Markers

Figures

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Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB	chemical treatment by environment: Cyclopamine	26+ somites	inner ear morphogenesis decreased process quality, abnormal	Fig 3
AB	chemical treatment by environment: Cyclopamine	26+ somites	otic vesicle anterior region fgf10a expression increased amount, abnormal	Fig 4
AB	chemical treatment by environment: Cyclopamine	26+ somites	otic vesicle development decreased process quality, abnormal	Fig 4
AB	chemical treatment by environment: Cyclopamine	26+ somites	otic vesicle posterior region hmx2 expression increased amount, abnormal	Fig 3
AB	chemical treatment by environment: Cyclopamine	26+ somites	otic vesicle posterior region hmx3a expression increased amount, abnormal	Fig 3
AB	chemical treatment by environment: Cyclopamine	26+ somites	pharyngeal pouch fgf3 expression absent, abnormal	Fig 4
AB	chemical treatment by environment: Cyclopamine	Prim-25	inner ear morphogenesis decreased process quality, abnormal	Fig 3
AB	chemical treatment by environment: Cyclopamine	Prim-25	otic sensory epithelium postero-lateral region increased thickness, abnormal	Fig 3
AB	chemical treatment by environment: Cyclopamine	Prim-25	otic vesicle development decreased process quality, abnormal	Fig 4
AB	chemical treatment by environment: Cyclopamine	Prim-25	otic vesicle posterior region fgf3 expression mislocalised, abnormal	Fig 4

1 - 10 of 96

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
b577		Point Mutation	smo
b641		Point Mutation	smo
hi1640Tg	Tg(nLacz-GTvirus)	Transgenic Insertion	smo
pt6Tg	Tg(dusp6:d2EGFP)	Transgenic Insertion
sh564Tg	Tg(hsp70l:hmx3a)	Transgenic Insertion
su3		Indel	hmx3a
t21142		Point Mutation	fgf3
ta52b		Point Mutation	mib1
w2		Point Mutation	mitfa
x17Tg	Tg1(hsp70l:fgf8a)	Transgenic Insertion

1 - 10 of 11

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
hmx3a	CRISPR2-hmx3a	CRISPR

Fish

Fish
AB
hmx3a^su3/su3 (AB)
mitfa^w2/w2; zf115Tg
sh564Tg
smo^{hi1640Tg/hi1640Tg}
x17Tg

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
d2EGFP	EFG	d2EGFP

Mapping

Hartwell et al., 2019 ZDB-PUB-190426-5 PMID:31022185

Anteroposterior patterning of the zebrafish ear through Fgf- and Hh-dependent regulation of hmx3a expression

Hartwell et al., 2019

ZDB-PUB-190426-5
PMID:31022185