PUBLICATION

Canonical Wnt signaling through Lef1 is required for hypothalamic neurogenesis

Authors

Lee, J.E., Wu, S.F., Goering, L.M., and Dorsky, R.I.

ID

ZDB-PUB-061020-59

Date

2006

Source

Development (Cambridge, England) 133(22): 4451-4461 (Journal)

Registered Authors

Dorsky, Richard, Lee, Ji Eun, Wu, Shan-Fu

Keywords

Zebrafish, Wnt, Lef1, Hypothalamus

MeSH Terms

SOXB1 Transcription Factors
Cell Differentiation/physiology*
Zebrafish/embryology*
Wnt Proteins/metabolism*
Wnt Proteins/physiology
Hypothalamus/embryology*
High Mobility Group Proteins/metabolism
Blotting, Western
In Situ Nick-End Labeling
Chromatin Immunoprecipitation
Reverse Transcriptase Polymerase Chain Reaction
Gene Expression Regulation, Developmental*
DNA Primers
Lymphoid Enhancer-Binding Factor 1/metabolism*
Animals
Immunohistochemistry
Transcription Factors/metabolism
In Situ Hybridization
DNA-Binding Proteins/metabolism
Signal Transduction/physiology*

(all 20)

PubMed

17050627 Full text @ Development

Abstract

Although the functional importance of the hypothalamus has been demonstrated throughout vertebrates, the mechanisms controlling neurogenesis in this forebrain structure are poorly understood. We report that canonical Wnt signaling acts through Lef1 to regulate neurogenesis in the zebrafish hypothalamus. We show that Lef1 is required for proneural and neuronal gene expression, and for neuronal differentiation in the posterior hypothalamus. Furthermore, we find that this process is dependent on Wnt8b, a ligand of the canonical pathway expressed in the posterior hypothalamus, and that both Wnt8b and Lef1 act to mediate beta-catenin-dependent transcription in this region. Finally, we show that Lef1 associates in vivo with the promoter of sox3, which depends on Lef1 for its expression and can rescue neurogenesis in the absence of Lef1. The conserved presence of this pathway in other vertebrates suggests a common mechanism for regulating hypothalamic neurogenesis.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
ascl1a	Df(Chr01:lef1,msxb)x8/x8	standard conditions	Prim-15	Not Detected	hypothalamus	ISH	Fig. S2
ascl1a	WT	standard conditions	Prim-5		forebrain	ISH	Fig. 2
ascl1a	WT	standard conditions	Prim-5		forebrain	ISH	Fig. 4
ascl1a	WT	standard conditions	Prim-5		hypothalamus	ISH	Fig. 4
ascl1a	WT	standard conditions	Prim-15		hypothalamus	ISH	Fig. 2
ascl1a	WT + MO2-lef1	standard conditions	Prim-5		forebrain	ISH	Fig. 4
ascl1a	WT + MO2-lef1	standard conditions	Prim-5	Not Detected	hypothalamus	ISH	Fig. 4
ascl1a	WT + MO2-wnt8b	standard conditions	Prim-15	Not Detected	hypothalamus	ISH	Fig. 7
dlx2a	Df(Chr01:lef1,msxb)x8/x8	standard conditions	Prim-15	Not Detected	hypothalamus	ISH	Fig. S2
dlx2a	WT	standard conditions	Prim-15		forebrain	ISH	Fig. 4

1 - 10 of 85

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO2-lef1	standard conditions	Prim-5 to Prim-15	forebrain neuron development disrupted, abnormal	Fig. 4
WT + MO2-lef1	standard conditions	Prim-5 to Prim-15	hypothalamus neuron morphology, abnormal	Fig. 4
WT + MO2-lef1	standard conditions	Prim-25	hypothalamus cell differentiation disrupted, abnormal	Fig. 5
WT + MO2-lef1	standard conditions	Prim-25	hypothalamus neuron decreased amount, abnormal	Fig. 5
WT + MO2-lef1	standard conditions	Long-pec	hypothalamus axon decreased amount, abnormal	Fig. 5
WT + MO2-wnt8b	standard conditions	Prim-15	forebrain neuron differentiation disrupted, abnormal	Fig. 7
WT + MO2-wnt8b	standard conditions	Prim-15	hypothalamus development disrupted, abnormal	Fig. 7
WT + MO2-wnt8b	standard conditions	Prim-15	hypothalamus posterior side morphology, abnormal	Fig. 1
WT + MO2-wnt8b	standard conditions	Prim-15	hypothalamus posterior side morphology, abnormal	Fig. 7

1 - 9 of 9

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
w25Tg	Tg(top:GFP)	Transgenic Insertion
x8		Deficiency	lef1 msx1b

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
lef1	MO2-lef1	MRPHLNO
wnt8b	MO2-wnt8b	MRPHLNO

Fish

Fish
Df(Chr01:lef1,msxb)x8/x8
w25Tg
WT
WT + MO2-lef1
WT + MO2-wnt8b

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab1-lef1	polyclonal	lef1		Rabbit

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
GFP	EFG	GFP

Mapping

Lee et al., 2006 ZDB-PUB-061020-59 PMID:17050627

Canonical Wnt signaling through Lef1 is required for hypothalamic neurogenesis

Lee et al., 2006

ZDB-PUB-061020-59
PMID:17050627