PUBLICATION

Sox2 is required for maintenance and regeneration, but not initial development, of hair cells in the zebrafish inner ear

Authors

Millimaki, B.B., Sweet, E.M., and Riley, B.B.

ID

ZDB-PUB-100105-8

Date

2010

Source

Developmental Biology 338(2): 262-269 (Journal)

Registered Authors

Riley, Bruce, Sweet, Elly

Keywords

Regeneration, Hair cell, Support cell, Zebrafish, Heat shock, Atoh1a, Fgf, Notch, Laser ablation

MeSH Terms

Animals
Hair Cells, Auditory/cytology*
SOXB1 Transcription Factors/genetics
SOXB1 Transcription Factors/physiology
Cell Survival
Regeneration*
Zebrafish
SOX Transcription Factors/genetics
SOX Transcription Factors/physiology*
Cell Differentiation
Gene Expression Regulation
Zebrafish Proteins/genetics
Zebrafish Proteins/physiology*
Ear, Inner/cytology*

(all 14)

PubMed

20025865 Full text @ Dev. Biol.

Abstract

Sox2 has been variously implicated in maintenance of pluripotent stem cells or, alternatively, early stages of cell differentiation, depending on context. In the developing inner ear, Sox2 initially marks all cells in the nascent sensory epithelium and, in mouse, is required for sensory epithelium formation. Sox2 is eventually downregulated in hair cells but is maintained in support cells, the functional significance of which is unknown. Here we describe regulation and function of sox2 in the zebrafish inner ear. Expression of sox2 begins after the onset of sensory epithelium development and is regulated by Atoh1a/b, Fgf and Notch. Knockdown of sox2 does not prevent hair cell production, but the rate of accumulation is reduced due to sporadic death of differentiated hair cells. We next tested the capacity for hair cell regeneration following laser ablation of mature brn3c:gfp-labeled hair cells. In control embryos, regeneration of lost hair cells begins by 12 h post-ablation and involves transdifferentiation of support cells rather than asymmetric cell division. In contrast, regeneration does not occur in sox2-depleted embryos. These data show that zebrafish sox2 is required for hair cell survival, as well as for transdifferentiation of support cells into hair cells during regeneration.

Genes / Markers

Figures

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Expression

Fish	Conditions	Stage	Anatomy	Assay	Figure
WT	standard conditions	Prim-15	macula saccule	ISH	Fig. 1
WT	standard conditions	Prim-15	macula utricle	ISH	Fig. 1
WT	standard conditions	10-13 somites	otic placode	ISH	Fig. 1
WT + MO2-sox2	standard conditions	Prim-15	macula saccule	ISH	Fig. 1
WT + MO2-sox2	standard conditions	Prim-15	macula utricle	ISH	Fig. 1
WT + MO2-sox2	standard conditions	10-13 somites	otic placode	ISH	Fig. 1
s356tTg	standard conditions	Long-pec	hair cell	IFL	Fig. 1
s356tTg	standard conditions	Prim-5	hair cell	IFL	Fig. 1
s356tTg	standard conditions	Pec-fin	hair cell	IFL	Fig. 1
s356tTg	standard conditions	Prim-5	hair cell anterior macula	IFL	Fig. 1

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO2-sox2	standard conditions	Long-pec	macula saccule cell death increased occurrence, abnormal	Fig. 2
WT + MO2-sox2	standard conditions	Long-pec	macula utricle cell death increased occurrence, abnormal	Fig. 2
s356tTg	standard conditions	Prim-15	macula utricle has fewer parts of type hair cell, abnormal	Fig. 1
s356tTg	standard conditions	Prim-25	macula utricle has fewer parts of type hair cell, abnormal	Fig. 1
s356tTg	standard conditions	Long-pec	inner ear receptor cell development increased duration, abnormal	Fig. 1
s356tTg	standard conditions	Long-pec	macula utricle has fewer parts of type hair cell, abnormal	Fig. 1
s356tTg	standard conditions	Pec-fin	hair cell anterior macula disorganized, abnormal	Fig. 1
s356tTg	standard conditions	Pec-fin	hair cell anterior macula protruding out of macula utricle, abnormal	Fig. 1
s356tTg	standard conditions	Pec-fin	inner ear receptor cell development increased duration, abnormal	Fig. 1
s356tTg; x20Tg	heat shock	Prim-15	optic vesicle hair cell displaced, abnormal	Fig. 3

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Mutations / Transgenics

Allele	Construct	Type
kca3Tg	Tg(5xUAS-E1B:6xMYC-notch1a)	Transgenic Insertion
kca4Tg	Tg(-1.5hsp70l:GAL4)	Transgenic Insertion
s356tTg	Tg(pou4f3:GAP-GFP)	Transgenic Insertion
x17Tg	Tg1(hsp70l:fgf8a)	Transgenic Insertion
x20Tg	Tg(hsp70l:atoh1a)	Transgenic Insertion
x21Tg	Tg(hsp70l:sox2)	Transgenic Insertion

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
atoh1a	MO4-atoh1a	MRPHLNO
atoh1b	MO1-atoh1b	MRPHLNO
sox2	MO2-sox2	MRPHLNO
tp53	MO4-tp53	MRPHLNO

Fish

Fish
kca3Tg/+; kca4Tg/+
s356tTg
s356tTg + MO2-sox2
s356tTg; x20Tg
s356tTg; x20Tg + MO2-sox2
s356tTg; x20Tg; x21Tg
s356tTg; x21Tg
WT
WT + MO1-atoh1b + MO4-atoh1a
WT + MO2-sox2

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
GAL4	EFG	GAL4
GFP	EFG	GFP

Mapping

Millimaki et al., 2010 ZDB-PUB-100105-8 PMID:20025865

Sox2 is required for maintenance and regeneration, but not initial development, of hair cells in the zebrafish inner ear

Millimaki et al., 2010

ZDB-PUB-100105-8
PMID:20025865