PUBLICATION

Two tcf3 genes cooperate to pattern the zebrafish brain

Authors

Dorsky, R.I., Itoh, M., Moon, R.T., and Chitnis, A.

ID

ZDB-PUB-030319-1

Date

2003

Source

Development (Cambridge, England) 130(9): 1937-1947 (Journal)

Registered Authors

Chitnis, Ajay, Dorsky, Richard, Itoh, Motoyuki, Moon, Randall T.

Keywords

none

MeSH Terms

Amino Acid Sequence
Animals
Brain/embryology*
Cytoskeletal Proteins
HMGB Proteins/genetics*
HMGB Proteins/metabolism
Molecular Sequence Data
Mutation
Phenotype
Proteins/metabolism
RNA, Antisense
TCF Transcription Factors
Transcription Factor 7-Like 1 Protein
Transcription Factors/genetics*
Transcription Factors/metabolism
Wnt Proteins
Zebrafish/embryology*
Zebrafish Proteins

(all 18)

PubMed

12642497 Full text @ Development

Abstract

Caudalizing factors operate in the context of Wnt/beta-catenin signaling to induce gene expression in discrete compartments along the rostral-caudal axis of the developing vertebrate nervous system. In zebrafish, basal repression of caudal genes is achieved through the function of Headless (Hdl), a Tcf3 homolog. In this study, we show that a second Tcf3 homolog, Tcf3b, limits caudalization caused by loss of Hdl function and although this Lef/Tcf family member can rescue hdl mutants, Lef1 cannot. Wnts can antagonize repression mediated by Tcf3 and this derepression is dependent on a Tcf3 beta-catenin binding domain. Systematic changes in gene expression caused by reduced Tcf3 function help predict the shape of a caudalizing activity gradient that defines compartments along the rostral-caudal axis. In addition, Tcf3b has a second and unique role in the morphogenesis of rhombomere boundaries, indicating that it controls multiple aspects of brain development.

Genes / Markers

Marker	Marker Type	Name
egr2b	GENE	early growth response 2b
en2a	GENE	engrailed homeobox 2a
foxb1a	GENE	forkhead box B1a
gbx1	GENE	gastrulation brain homeobox 1
gsc	GENE	goosecoid
isl1a	GENE	ISL LIM homeobox 1a
pax2a	GENE	paired box 2a
pax6a	GENE	paired box 6a
tcf7l1a	GENE	transcription factor 7 like 1a
tcf7l1b	GENE	transcription factor 7 like 1b

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Figures

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Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-tcf7l1a	standard conditions	Protruding-mouth	eye aplastic, abnormal	Fig. 3
WT + MO1-tcf7l1a	standard conditions	Protruding-mouth	telencephalon aplastic, abnormal	Fig. 3
WT + MO1-tcf7l1a + MO1-tcf7l1b	standard conditions	Protruding-mouth	brain decreased size, abnormal	Fig. 3
WT + MO1-tcf7l1a + MO1-tcf7l1b	standard conditions	Protruding-mouth	eye aplastic, abnormal	Fig. 3
WT + MO1-tcf7l1a + MO1-tcf7l1b	standard conditions	Protruding-mouth	head decreased size, abnormal	Fig. 3
WT + MO1-tcf7l1a + MO1-tcf7l1b	standard conditions	Protruding-mouth	telencephalon aplastic, abnormal	Fig. 3
WT + MO1-tcf7l1b	standard conditions	Prim-5	midbrain hindbrain boundary closure incomplete, abnormal	Fig. 6
WT + MO1-tcf7l1b	standard conditions	Prim-5	rhombomere morphogenesis disrupted, abnormal	Fig. 6
WT + MO1-tcf7l1b	standard conditions	Prim-5	rhombomere morphology, abnormal	Fig. 6
WT + MO1-tcf7l1b	standard conditions	Protruding-mouth	brain decreased size, abnormal	Fig. 3

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
m881		Point Mutation	tcf7l1a

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
tcf7l1a	MO1-tcf7l1a	MRPHLNO
tcf7l1b	MO1-tcf7l1b	MRPHLNO
wnt8a	MO1-wnt8a	MRPHLNO
wnt8a	MO2-wnt8a	MRPHLNO

Fish

Fish
tcf7l1a^m881/m881
tcf7l1a^m881/m881 + MO1-tcf7l1b
WT + MO1-tcf7l1a
WT + MO1-tcf7l1a + MO1-tcf7l1b
WT + MO1-tcf7l1b

Antibodies

Orthology

Gene	Orthology
tcf7l1a
tcf7l1b

Engineered Foreign Genes

Mapping

Dorsky et al., 2003 ZDB-PUB-030319-1 PMID:12642497

Two tcf3 genes cooperate to pattern the zebrafish brain

Dorsky et al., 2003

ZDB-PUB-030319-1
PMID:12642497