PUBLICATION

Jag1b is essential for patterning inner ear sensory cristae by regulating anterior morphogenetic tissue separation and preventing posterior cell death

Authors

Ma, W.R., Zhang, J.

ID

ZDB-PUB-150127-12

Date

2015

Source

Development (Cambridge, England) 142(4): 763-73 (Journal)

Registered Authors

Ma, Weirui, Zhang, Jian

Keywords

Jag1b, Inner ear, Cristae, Notch, FGF, Cell death, Zebrafish

MeSH Terms

Morphogenesis/genetics
Morphogenesis/physiology*
Calcium-Binding Proteins/genetics
Calcium-Binding Proteins/metabolism*
Intercellular Signaling Peptides and Proteins/genetics
Intercellular Signaling Peptides and Proteins/metabolism*
Fibroblast Growth Factor 10
Membrane Proteins/genetics
Membrane Proteins/metabolism*
Body Patterning/genetics
Body Patterning/physiology
Animals
Zebrafish
Signal Transduction/genetics
Signal Transduction/physiology
Ear, Inner/embryology*
Ear, Inner/metabolism*
Cell Death/genetics
Cell Death/physiology
Receptors, Notch/genetics
Receptors, Notch/metabolism
Zebrafish Proteins
Gene Expression Regulation, Developmental

(all 23)

PubMed

25617438 Full text @ Development

Abstract

The sensory patches of the vertebrate inner ear, which contain hair cells and supporting cells, are essential for hearing and balance functions. How the stereotypically organized sensory patches are formed remains to be determined. In this study, we isolated a zebrafish mutant in which the jag1b gene is disrupted by an EGFP insertion. Loss of Jag1b causes cell death in the developing posterior crista and results in downregulation of fgf10a in the posterior prosensory cells. Inhibition of FGFR activity in wild-type embryos also causes loss of the posterior crista, suggesting that Fgf10a mediates Jag1b activity. By contrast, in the anterior prosensory domain, Jag1b regulates separation of a single morphogenetic field into anterior and lateral cristae by flattening cells destined to form a nonsensory epithelium between the two cristae. MAPK activation in the nonsensory epithelium precursors is required for the separation. In the jag1b mutant, MAPK activation and cell flattening are extended to anterior crista primordia, causing loss of anterior crista. More importantly, inhibition of MAPK activity, which blocks the differentiation of nonsensory epithelial cells, generated a fused large crista and extra hair cells. Thus, Jag1b uses two distinct mechanisms to form three sensory cristae in zebrafish.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
bmp2b	jag1b^gd2Gt/gd2Gt	standard conditions	Prim-5	otic vesicle	ISH	Fig. S4
bmp2b	jag1b^gd2Gt/+	standard conditions	Prim-5	otic vesicle	ISH	Fig. S4
bmp2b	WT	standard conditions	Prim-5	otic vesicle	ISH	Fig. S4
bmp4	jag1b^gd2Gt/gd2Gt	standard conditions	Prim-5	otic vesicle	ISH	Fig. S4
bmp4	jag1b^gd2Gt/gd2Gt	standard conditions	Prim-5	otic vesicle	ISH	Fig. 3
bmp4	jag1b^gd2Gt/+	standard conditions	Prim-5	otic vesicle	ISH	Fig. S4
bmp4	jag1b^gd2Gt/+	standard conditions	Prim-5	otic vesicle	ISH	Fig. 3
bmp4	WT	control	Prim-5	otic vesicle	ISH	Fig. S4
bmp4	WT	control	Prim-5	otic vesicle	ISH	Fig. 3
cdh1	jag1b^gd2Gt/gd2Gt	standard conditions	Prim-25	otic vesicle epithelial cell	IHC	Fig. 5

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
jag1b^gd2Gt/gd2Gt	standard conditions	Prim-15	otic vesicle posterior crista apoptotic, abnormal	Fig. 3
jag1b^gd2Gt/gd2Gt	standard conditions	Prim-25	otic vesicle posterior crista apoptotic, abnormal	Fig. 3
jag1b^gd2Gt/gd2Gt	standard conditions	Long-pec	anterior macula present, normal	Fig. 2
jag1b^gd2Gt/gd2Gt	standard conditions	Long-pec	otic vesicle anterior crista absent, abnormal	Fig. 2
jag1b^gd2Gt/gd2Gt	standard conditions	Long-pec	otic vesicle anterior crista absent, abnormal	Fig. 3
jag1b^gd2Gt/gd2Gt	standard conditions	Long-pec	otic vesicle posterior crista absent, abnormal	Fig. 2
jag1b^gd2Gt/gd2Gt	standard conditions	Long-pec	otic vesicle posterior crista absent, abnormal	Fig. 3
jag1b^gd2Gt/gd2Gt	standard conditions	Long-pec	posterior macula present, normal	Fig. 2
jag1b^gd2Gt/gd2Gt	standard conditions	Protruding-mouth	anterior macula present, normal	Fig. 2
jag1b^gd2Gt/gd2Gt	standard conditions	Protruding-mouth	otic vesicle anterior crista absent, abnormal	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
gd2Gt	Gt2(bcl2a-EGFP)	Transgenic Insertion	jag1b

Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
jag1b^gd2Gt/gd2Gt
jag1b^gd2Gt/+
WT

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab1-jag1	polyclonal		IgG	Rabbit

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Ma et al., 2015 ZDB-PUB-150127-12 PMID:25617438

Jag1b is essential for patterning inner ear sensory cristae by regulating anterior morphogenetic tissue separation and preventing posterior cell death

Ma et al., 2015

ZDB-PUB-150127-12
PMID:25617438