PUBLICATION

Positional cloning of the young mutation identifies an essential role for the Brahma chromatin remodeling complex in mediating retinal cell differentiation

Authors

Gregg, R.G., Willer, G.B., Fadool, J.M., Dowling, J.E., and Link, B.A.

ID

ZDB-PUB-030527-14

Date

2003

Source

Proceedings of the National Academy of Sciences of the United States of America 100(11): 6535-6540 (Journal)

Registered Authors

Dowling, John E., Fadool, James M., Gregg, Ronald G., Link, Brian, Willer, Greg

Keywords

none

MeSH Terms

Trans-Activators/genetics*
Molecular Sequence Data
Cell Cycle Proteins/genetics*
Mutation*
DNA Primers
Drosophila Proteins
Animals
Chromatin/metabolism*
Cloning, Molecular
Base Sequence
Zebrafish/embryology

(all 11)

PubMed

12748389 Full text @ Proc. Natl. Acad. Sci. USA

Abstract

Zebrafish with the young (yng) mutation show a defect in retinal cell differentiation. Here we demonstrate that a mutation in a brahma-related gene (brg1) is responsible for the yng phenotype. Brahma homologues function as essential subunits for SWI/SNF-type chromatin remodeling complexes. Our analysis indicates that brg1 is required for the wave of mitogen-activated protein kinase activity that precedes retinal cell differentiation. Using specific inhibitors of the mitogen-activated protein kinase pathway we show this signal has a direct role in retinal cell differentiation. Lastly, through investigations of mutants in other chromatin remodeling subunits, we provide genetic evidence for gene and tissue specificity of the Brahma chromatin remodeling complex.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
atoh7	smarca4a^a8/a8 (AB)	standard conditions	Protruding-mouth	retina	ISH	Fig. 3
atoh7	smarca4a^a8/a8 (AB)	standard conditions	Day 4	retina	ISH	Fig. 3
atoh7	smarca4a^a8/a8 (AB)	standard conditions	Prim-15	retina	ISH	Fig. 3
atoh7	WT	standard conditions	Prim-15	retina	ISH	Fig. 3
atoh7	WT	standard conditions	Protruding-mouth	retina	ISH	Fig. 3
atoh7	WT	standard conditions	Day 4	retina	ISH	Fig. 3
shha	smarca4a^a8/a8 (AB)	standard conditions	Day 4	retina	ISH	Fig. 3
shha	WT	standard conditions	Long-pec	retina	ISH	Fig. 3
smarca4a	WT	standard conditions	Prim-5	brain	ISH	Fig. 1
smarca4a	WT	standard conditions	Long-pec	brain	ISH	Fig. 1

1 - 10 of 16

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-smarca4a	standard conditions	Protruding-mouth	ear development disrupted, abnormal	text only
WT + MO1-smarca4a	standard conditions	Protruding-mouth	fin development disrupted, abnormal	text only
WT + MO1-smarca4a	standard conditions	Protruding-mouth	fin morphology, abnormal	text only
WT + MO1-smarca4a	standard conditions	Protruding-mouth	heart morphogenesis disrupted, abnormal	text only
WT + MO1-smarca4a	standard conditions	Protruding-mouth	heart morphology, abnormal	text only
WT + MO1-smarca4a	standard conditions	Protruding-mouth	inner ear morphology, abnormal	text only
WT + MO1-smarca4a	standard conditions	Protruding-mouth	melanocyte decreased amount, abnormal	text only
WT + MO1-smarca4a	standard conditions	Protruding-mouth	retina layer formation arrested, abnormal	text only
WT + MO1-smarca4a	standard conditions	Protruding-mouth	retina structure, abnormal	text only
WT + MO2-smarca4a	standard conditions	Protruding-mouth	ear development disrupted, abnormal	Fig. 2

1 - 10 of 30

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
a8		Point Mutation	smarca4a
hi550Tg	Tg(F5)	Transgenic Insertion	smarca5
hi1072Tg	Tg(nLacz-GTvirus)	Transgenic Insertion	actl6a

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
smarca4a	MO1-smarca4a	MRPHLNO
smarca4a	MO2-smarca4a	MRPHLNO

Fish

Fish
actl6a^{hi1072Tg/hi1072Tg}
smarca4a^a8/a8 (AB)
smarca5^{hi550Tg/hi550Tg}
WT
WT + MO1-smarca4a
WT + MO2-smarca4a

Antibodies

Orthology

Gene	Orthology
smarca4a

Engineered Foreign Genes

Mapping

Entity Type	Entity Symbol	Location
Feature	a8	Chr: 3 Details
SSLP	z1140	Chr: 3 Details
SSLP	z5623	Chr: 3 Details

Gregg et al., 2003 ZDB-PUB-030527-14 PMID:12748389

Positional cloning of the young mutation identifies an essential role for the Brahma chromatin remodeling complex in mediating retinal cell differentiation

Gregg et al., 2003

ZDB-PUB-030527-14
PMID:12748389