PUBLICATION

Fgf8 is mutated in zebrafish acerebellar (ace) mutants and is required for maintenance of midbrain-hindbrain boundary development and somitogenesis

Authors

Reifers, F., Bohli, H., Walsh, E.C., Crossley, P.H., Stainier, D.Y., and Brand, M.

ID

ZDB-PUB-980810-27

Date

1998

Source

Development (Cambridge, England) 125: 2381-2395 (Journal)

Registered Authors

Brand, Michael, Reifers, Frank, Stainier, Didier, Walsh, Emily

Keywords

none

MeSH Terms

Crosses, Genetic
Zebrafish
Heterozygote
Amino Acid Sequence
Gastrula/physiology
Fibroblast Growth Factor 8
Molecular Sequence Data
Somites
Mutation
Gene Expression Regulation, Developmental
Blastoderm/physiology
Embryonic Induction/genetics
Sequence Alignment
Mice
Sequence Homology, Amino Acid
Animals
Chickens
Cerebellum/abnormalities
Humans
RNA Probes
Body Patterning/genetics*
Cloning, Molecular
Brain/abnormalities
Brain/embryology*
Fibroblast Growth Factors/deficiency
Fibroblast Growth Factors/genetics*
Fibroblast Growth Factors/physiology*

(all 27)

PubMed

9609821 Full text @ Development

Abstract

We describe the isolation of zebrafish Fgf8 and its expression during gastrulation, somitogenesis, fin bud and early brain development. By demonstrating genetic linkage and by analysing the structure of the Fgf8 gene, we show that acerebellar is a zebrafish Fgf8 mutation that may inactivate Fgf8 function. Homozygous acerebellar embryos lack a cerebellum and the midbrain-hindbrain boundary organizer. Fgf8 function is required to maintain, but not initiate, expression of Pax2.1 and other marker genes in this area. We show that Fgf8 and Pax2.1 are activated in adjacent domains that only later become overlapping, and activation of Fgf8 occurs normally in no isthmus embryos that are mutant for Pax2.1. These findings suggest that multiple signaling pathways are independently activated in the midbrain-hindbrain boundary primordium during gastrulation, and that Fgf8 functions later during somitogenesis to polarize the midbrain. Fgf8 is also expressed in a dorsoventral gradient during gastrulation and ectopically expressed Fgf8 can dorsalize embryos. Nevertheless, acerebellar mutants show only mild dorsoventral patterning defects. Also, in spite of the prominent role suggested for Fgf8 in limb development, the pectoral fins are largely unaffected in the mutants. Fgf8 is therefore required in development of several important signaling centers in the zebrafish embryo, but may be redundant or dispensable for others.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
egr2b	WT	standard conditions	Bud		presumptive rhombomere 3	ISH	Fig. 3
egr2b	WT	standard conditions	5-9 somites		presumptive rhombomere 3	ISH	Fig. 3
egr2b	WT	standard conditions	Bud		presumptive rhombomere 5	ISH	Fig. 3
egr2b	WT	standard conditions	5-9 somites		presumptive rhombomere 5	ISH	Fig. 3
en1a	fgf8a^{ti282a/ti282a}	standard conditions	Prim-25		pectoral fin bud antero-ventral region	ISH	Fig. 11
en1a	WT	standard conditions	Prim-25		pectoral fin bud antero-ventral region	ISH	Fig. 11
en1a	WT	standard conditions	Prim-15		pectoral fin bud antero-ventral region	ISH	Fig. 11
en2a	fgf8a^{ti282a/ti282a}	standard conditions	Prim-5	Not Detected	midbrain hindbrain boundary	ISH	Fig. 8
en2a	fgf8a^{ti282a/ti282a}	standard conditions	5-9 somites		midbrain hindbrain boundary neural keel	ISH	Fig. 8
en2a	fgf8a^{ti282a/ti282a}	standard conditions	10-13 somites		midbrain hindbrain boundary neural keel	ISH	Fig. 8

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
fgf8a^{ti282a/ti282a}	standard conditions	75%-epiboly	somite development decreased process quality, abnormal	Fig. 10
fgf8a^{ti282a/ti282a}	standard conditions	Bud	somite development decreased process quality, abnormal	Fig. 10
fgf8a^{ti282a/ti282a}	standard conditions	5-9 somites	intermediate mesoderm differentiated, normal	Fig. 10
fgf8a^{ti282a/ti282a}	standard conditions	5-9 somites	midbrain hindbrain boundary physical object quality, abnormal	Fig. 8
fgf8a^{ti282a/ti282a}	standard conditions	5-9 somites	midbrain-hindbrain boundary development decreased process quality, abnormal	Fig. 8
fgf8a^{ti282a/ti282a}	standard conditions	10-13 somites	midbrain hindbrain boundary physical object quality, abnormal	Fig. 8
fgf8a^{ti282a/ti282a}	standard conditions	10-13 somites	midbrain-hindbrain boundary development decreased process quality, abnormal	Fig. 8
fgf8a^{ti282a/ti282a}	standard conditions	10-13 somites	somite development decreased process quality, abnormal	Fig. 10
fgf8a^{ti282a/ti282a}	standard conditions	10-13 somites	somite poorly differentiated, abnormal	Fig. 10
fgf8a^{ti282a/ti282a}	standard conditions	20-25 somites	somite development decreased process quality, abnormal	Fig. 10

1 - 10 of 27

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ti282a		Point Mutation	fgf8a
tu29a		Point Mutation	pax2a

Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
fgf8a^{ti282a/ti282a}
pax2a^tu29a/tu29a
WT

Antibodies

Orthology

Gene	Orthology
fgf8a

Engineered Foreign Genes

Mapping

Reifers et al., 1998 ZDB-PUB-980810-27 PMID:9609821

Fgf8 is mutated in zebrafish acerebellar (ace) mutants and is required for maintenance of midbrain-hindbrain boundary development and somitogenesis

Reifers et al., 1998

ZDB-PUB-980810-27
PMID:9609821