PUBLICATION

Hh and Wnt signaling regulate formation of olig2(+) neurons in the zebrafish cerebellum

Authors

McFarland, K.A., Topczewska, J.M., Weidinger, G., Dorsky, R.I., and Appel, B.

ID

ZDB-PUB-080422-14

Date

2008

Source

Developmental Biology 318(1): 162-171 (Journal)

Registered Authors

Appel, Bruce, Dorsky, Richard, McFarland, Karen, Topczewska, Jolanta, Weidinger, Gilbert

Keywords

Cerebellum, Purkinje neuron, Eurydendroid neuron, Hedgehog, Wnt, Zebrafish, Dorsoventral, olig2

MeSH Terms

Receptors, G-Protein-Coupled/genetics
Receptors, G-Protein-Coupled/metabolism
Nerve Tissue Proteins/genetics
Nerve Tissue Proteins/metabolism*
Neurons/cytology
Neurons/physiology*
S100 Calcium Binding Protein G/genetics
S100 Calcium Binding Protein G/metabolism
Animals, Genetically Modified
Morphogenesis
Veratrum Alkaloids/metabolism
Genes, Reporter
Calbindin 2
Hedgehog Proteins/genetics
Hedgehog Proteins/metabolism*
Basic Helix-Loop-Helix Transcription Factors/genetics
Basic Helix-Loop-Helix Transcription Factors/metabolism*
Signal Transduction*
Gene Expression Regulation, Developmental
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Animals
Wnt Proteins/genetics
Wnt Proteins/metabolism*
Zebrafish/anatomy & histology
Zebrafish/embryology*
Zebrafish/metabolism
Cerebellum/cytology
Cerebellum/embryology*
Intercellular Signaling Peptides and Proteins/genetics
Intercellular Signaling Peptides and Proteins/metabolism

(all 31)

PubMed

18423594 Full text @ Dev. Biol.

Abstract

The cerebellum, which forms from anterior hindbrain, coordinates motor movements and balance. Sensory input from the periphery is relayed and modulated by cerebellar interneurons, which are organized in layers. The mechanisms that specify the different neurons of the cerebellum and direct its layered organization remain poorly understood. Drawing from investigations of spinal cord, we hypothesized that the embryonic cerebellum is patterned on the dorsoventral axis by opposing morphogens. We tested this using zebrafish. Here we show that expression of olig2, which encodes a bHLH transcription factor, marks a distinct subset of neurons with similarities to eurydendroid neurons, the principal efferent neurons of the teleost cerebellum. In combination with other markers, olig2 reveals a dorsoventral organization of cerebellar neurons in embryos. Disruption of Hedgehog signaling, which patterns the ventral neural tube, produced a two-fold increase in the number of olig2(+) neurons. By contrast, olig2(+) neurons did not develop in embryos deficient for Wnt signaling, which patterns dorsal neural tube, nor did they develop in embryos deficient for both Hedgehog and Wnt signaling. Our data indicate that Hedgehog and Wnt work in opposition across the dorsoventral axis of the cerebellum to regulate formation of olig2(+) neurons. Specifically, we propose that Hedgehog limits the range of Wnt signaling, which is necessary for olig2(+) neuron development.

Genes / Markers

Figures

Show all Figures

Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
Df(Chr01:lef1,msxb)x8/x8	standard conditions	Long-pec	cerebellum physical object quality, abnormal	Fig. S2
Df(Chr01:lef1,msxb)x8/x8	standard conditions	Long-pec	cerebellum physical object quality, abnormal	Fig. 6
Df(Chr01:lef1,msxb)x8/x8	chemical treatment: Cyclopamine	Long-pec	cerebellum physical object quality, abnormal	Fig. 6
Df(Chr01:lef1,msxb)x8/x8	chemical treatment: Cyclopamine	Long-pec	spinal cord physical object quality, abnormal	Fig. 6
WT	chemical treatment: Cyclopamine	Long-pec	cerebellum increased thickness, abnormal	Fig. S1
WT	chemical treatment: Cyclopamine	Long-pec	midbrain hindbrain boundary physical object quality, abnormal	Fig. 7
smo^b641/b641	standard conditions	Long-pec	cerebellum physical object quality, abnormal	Fig. 3
smo^b641/b641	standard conditions	Long-pec	spinal cord physical object quality, abnormal	Fig. 3
w32Tg/w32Tg	heat shock, chemical treatment: Cyclopamine	Long-pec	cerebellum physical object quality, abnormal	Fig. 6
w32Tg/w32Tg	heat shock, chemical treatment: Cyclopamine	Long-pec	midbrain hindbrain boundary physical object quality, abnormal	Fig. 7

1 - 10 of 12

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
b641		Point Mutation	smo
vu12Tg	Tg(olig2:EGFP)	Transgenic Insertion
w32Tg	Tg(hsp70l:dkk1b-GFP)	Transgenic Insertion
x8		Deficiency	lef1 msx1b

Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
Df(Chr01:lef1,msxb)x8/x8
smo^b641/b641
vu12Tg
w32Tg/w32Tg
WT

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GFP	EFG	GFP

Mapping

McFarland et al., 2008 ZDB-PUB-080422-14 PMID:18423594

Hh and Wnt signaling regulate formation of olig2(+) neurons in the zebrafish cerebellum

McFarland et al., 2008

ZDB-PUB-080422-14
PMID:18423594