PUBLICATION

sox2 and sox3 play unique roles in development of hair cells and neurons in the zebrafish inner ear

Authors

Gou, Y., Vemaraju, S., Sweet, E.M., Kwon, H.J., Riley, B.B.

ID

ZDB-PUB-180123-5

Date

2018

Source

Developmental Biology 435(1): 73-83 (Journal)

Registered Authors

Kwon, Hye-Joo, Riley, Bruce, Sweet, Elly, Vemaraju, Shruti

Keywords

SoxB1, otic placode, sensory epithelia, statoacoustic ganglion

MeSH Terms

PAX2 Transcription Factor/genetics
PAX2 Transcription Factor/metabolism
Fibroblast Growth Factors/genetics
Fibroblast Growth Factors/metabolism
Neurogenesis/physiology*
Zebrafish/embryology*
Gene Expression Regulation, Developmental/physiology*
SOX Transcription Factors/biosynthesis*
SOX Transcription Factors/genetics
Receptors, Notch/genetics
Receptors, Notch/metabolism
Animals
Zebrafish Proteins/biosynthesis*
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism
Hair Cells, Auditory, Inner/cytology
Hair Cells, Auditory, Inner/metabolism*

(all 17)

PubMed

29355523 Full text @ Dev. Biol.

Abstract

Formation of neural and sensory progenitors in the inner ear requires Sox2 in mammals, and in other species is thought to rely on both Sox2 and Sox3. How Sox2 and/or Sox3 promote different fates is poorly understood. Our mutant analysis in zebrafish showed that sox2 is uniquely required for sensory development while sox3 is uniquely required for neurogenesis. Moderate misexpression of sox2 during placodal stages led to development of otic vesicles with expanded sensory and reduced neurogenic domains. However, high-level misexpression of sox2 or sox3 expanded both sensory and neurogenic domains to fill the medial and lateral halves of the otic vesicle, respectively. Disruption of medial factor pax2a eliminated the ability of sox2/3 misexpression to expand sensory but not neurogenic domains. Additionally, mild misexpression of fgf8 during placodal development was sufficient to specifically expand the zone of prosensory competence. Later, cross-repression between atoh1a and neurog1 helps maintain the sensory-neural boundary, but unlike mouse this does not require Notch activity. Together, these data show that sox2 and sox3 exhibit intrinsic differences in promoting sensory vs. neural competence, but at high levels these factors can mimic each other to enhance both states. Regional cofactors like pax2a and fgf8 also modify sox2/3 functions.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
atoh1a	AB	standard conditions	Prim-5	macula utricle	ISH	Fig. 1
atoh1a	AB	control	Prim-15	otic vesicle	ISH	Fig. 9
atoh1a	AB	control	Prim-5	otic vesicle	ISH	Fig. 9
atoh1a	AB	control	Prim-5	otic vesicle	ISH	Fig. 3
atoh1a	AB	control	Prim-5	otic vesicle	ISH	Fig. 4
atoh1a	AB	control	14-19 somites	otic vesicle	ISH	Fig. 5
atoh1a	AB	control	Prim-5	otic vesicle	ISH	Fig. 8
atoh1a	AB	control	Prim-5	otic vesicle	ISH	Fig. 2
atoh1a	AB + MO1-pax2a + MO4-tp53	standard conditions	Prim-5	otic vesicle	ISH	Fig. 8
atoh1a	mib1^ta52b/ta52b	standard conditions	Prim-5	otic vesicle	ISH	Fig. 9

1 - 10 of 81

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
mib1^ta52b/ta52b	standard conditions	Prim-5	otic vesicle atoh1a expression increased amount, abnormal	Fig. 9
mib1^ta52b/ta52b	standard conditions	Prim-5	otic vesicle atoh1a expression increased distribution, abnormal	Fig. 9
mib1^ta52b/ta52b	standard conditions	Prim-5	otic vesicle atoh1a expression spatial pattern, abnormal	Fig. 9
mib1^ta52b/ta52b	standard conditions	Prim-5	otic vesicle neurog1 expression increased amount, abnormal	Fig. 9
mib1^ta52b/ta52b	standard conditions	Prim-5	otic vesicle neurog1 expression increased distribution, abnormal	Fig. 9
mib1^ta52b/ta52b	standard conditions	Prim-5	otic vesicle neurog1 expression spatial pattern, abnormal	Fig. 9
sox2^x50/x50 (AB)	standard conditions	Prim-25	auditory receptor cell decreased amount, abnormal	Fig. 2
sox2^x50/x50; sox3^x52/x52 (AB)	standard conditions	Prim-25	auditory receptor cell decreased amount, abnormal	Fig. 2
sox2^x50/x50; sox3^x52/x52 (AB)	standard conditions	Prim-25	statoacoustic (VIII) ganglion neuron decreased amount, abnormal	Fig. 2
sox3^x52/x52 (AB)	standard conditions	Prim-25	statoacoustic (VIII) ganglion neuron decreased amount, abnormal	Fig. 2

1 - 10 of 113

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
s356tTg	Tg(pou4f3:GAP-GFP)	Transgenic Insertion
ta52b		Point Mutation	mib1
x17Tg	Tg1(hsp70l:fgf8a)	Transgenic Insertion
x20Tg	Tg(hsp70l:atoh1a)	Transgenic Insertion
x21Tg	Tg(hsp70l:sox2)	Transgenic Insertion
x28Tg	Tg2(hsp70l:neurog1)	Transgenic Insertion
x32Tg	Tg(hsp70l:sox3)	Transgenic Insertion
x50		Small Deletion	sox2
x52		Small Deletion	sox3

1 - 9 of 9

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
pax2a	MO1-pax2a	MRPHLNO
tp53	MO4-tp53	MRPHLNO

Fish

Fish
AB
AB + MO1-pax2a + MO4-tp53
mib1^ta52b/ta52b
sox2^x50/x50 (AB)
sox2^x50/x50; sox3^x52/x52 (AB)
sox3^x52/x52 (AB)
x17Tg/+ (AB)
x20Tg/+ (AB)
x21Tg/+
x21Tg/+ (AB)

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
GFP	EFG	GFP

Mapping

Gou et al., 2018 ZDB-PUB-180123-5 PMID:29355523

sox2 and sox3 play unique roles in development of hair cells and neurons in the zebrafish inner ear

Gou et al., 2018

ZDB-PUB-180123-5
PMID:29355523