PUBLICATION

The zebrafish zic2a-zic5 gene pair acts downstream of canonical Wnt signaling to control cell proliferation in the developing tectum

Authors

Nyholm, M.K., Wu, S.F., Dorsky, R.I., and Grinblat, Y.

ID

ZDB-PUB-070122-30

Date

2007

Source

Development (Cambridge, England) 134(4): 735-746 (Journal)

Registered Authors

Dorsky, Richard, Grinblat, Yevgenya, Nyholm, Molly Wagner, Wu, Shan-Fu

Keywords

Zic, Wnt, Proliferation, Tectum, Zebrafish

MeSH Terms

Wnt Proteins/physiology*
Mesencephalon/cytology
Mesencephalon/embryology
Mesencephalon/growth & development
Tectum Mesencephali/cytology
Tectum Mesencephali/embryology
Tectum Mesencephali/growth & development*
Embryo, Nonmammalian
Animals
Signal Transduction
Transcriptional Activation
DNA-Binding Proteins/genetics*
DNA-Binding Proteins/physiology
Body Patterning
Zebrafish
Cell Proliferation
Zebrafish Proteins/genetics*
Zebrafish Proteins/physiology

(all 18)

PubMed

17215296 Full text @ Development

Abstract

Wnt growth factors acting through the canonical intracellular signaling cascade play fundamental roles during vertebrate brain development. In particular, canonical Wnt signaling is crucial for normal development of the dorsal midbrain, the future optic tectum. Wnts act both as patterning signals and as regulators of cell growth. In the developing tectum, Wnt signaling is mitogenic; however, the mechanism of Wnt function is not known. As a step towards better understanding this mechanism, we have identified two new Wnt targets, the closely linked zic2a and zic5 genes. Using a combination of in vivo assays, we show that zic2a and zic5 transcription is activated by Tcf/Lef transcription factors in the dorsal midbrain. Zic2a and Zic5, in turn, have essential, cooperative roles in promoting cell proliferation in the tectum, but lack obvious patterning functions. Collectively these findings suggest that Wnts control midbrain proliferation, at least in part, through regulation of two novel target genes, the zic2a-zic5 gene pair.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
dbx1a	WT	control	Prim-5	basal plate midbrain region	ISH	Fig. 8
dbx1a	WT + MO1-zic5 + MO3-zic2a	standard conditions	Prim-5	basal plate midbrain region	ISH	Fig. 8
dlx3b	WT	standard conditions	90%-epiboly	non neural ectoderm	ISH	Fig. 1
dlx3b	WT	standard conditions	Shield	presumptive ectoderm	ISH	Fig. 1
pax7a	WT	control	14-19 somites	alar plate midbrain region	ISH	Fig. 8
pax7a	WT	control	Prim-5	alar plate midbrain region	ISH	Fig. 8
pax7a	WT	control	14-19 somites	midbrain	IHC	Fig. 9
pax7a	WT + MO1-zic5 + MO3-zic2a	standard conditions	Prim-5	alar plate midbrain region	ISH	Fig. 8
pax7a	WT + MO1-zic5 + MO3-zic2a	standard conditions	14-19 somites	alar plate midbrain region	ISH	Fig. 8
pax7a	WT + MO1-zic5 + MO3-zic2a	standard conditions	14-19 somites	midbrain	IHC	Fig. 9

1 - 10 of 93

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-tcf7	standard conditions	14-19 somites	brain wholly posteriorized, abnormal	Fig. 6
WT + MO1-tcf7	standard conditions	14-19 somites	midbrain morphology, abnormal	Fig. 6
WT + MO1-tcf7l1b + MO2-tcf7l1a	standard conditions	14-19 somites	forebrain wholly posteriorized, abnormal	Fig. 6
WT + MO1-tcf7l1b + MO2-tcf7l1a	standard conditions	14-19 somites	midbrain decreased size, abnormal	Fig. 6
WT + MO1-tcf7l1b + MO2-tcf7l1a	standard conditions	14-19 somites	midbrain increased size, abnormal	Fig. S4
WT + MO1-zic2a + MO2-zic2a	standard conditions	Prim-5	hindbrain malformed, abnormal	Fig. 7
WT + MO1-zic2a + MO2-zic2a	standard conditions	Prim-5	midbrain malformed, abnormal	Fig. 7
WT + MO1-zic5	standard conditions	Prim-5	fourth ventricle malformed, abnormal	text only
WT + MO1-zic5	standard conditions	Prim-5	tectal ventricle malformed, abnormal	text only
WT + MO1-zic5 + MO3-zic2a	standard conditions	14-19 somites	cell proliferation in midbrain disrupted, abnormal	Fig. 9

1 - 10 of 25

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Mutations / Transgenics

Allele	Construct	Type
uw2Tg	TgBAC(zic2a:GFP)	Transgenic Insertion
w25Tg	Tg(top:GFP)	Transgenic Insertion
w26Tg	Tg(hsp70l:tcf7l1a-GFP)	Transgenic Insertion

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
lef1	MO2-lef1	MRPHLNO
tcf7	MO1-tcf7	MRPHLNO
tcf7l1a	MO2-tcf7l1a	MRPHLNO
tcf7l1b	MO1-tcf7l1b	MRPHLNO
zic2a	MO1-zic2a	MRPHLNO
zic2a	MO2-zic2a	MRPHLNO
zic2a	MO3-zic2a	MRPHLNO
zic5	MO1-zic5	MRPHLNO

1 - 8 of 8

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Fish

Fish
uw2Tg
uw2Tg; w26Tg
w25Tg
w26Tg (AB)
WT
WT + MO1-tcf7
WT + MO1-tcf7l1b + MO2-tcf7l1a
WT + MO1-tcf7 + MO2-lef1
WT + MO1-zic2a + MO2-zic2a
WT + MO1-zic5

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GFP	EFG	GFP

Mapping

Nyholm et al., 2007 ZDB-PUB-070122-30 PMID:17215296

The zebrafish zic2a-zic5 gene pair acts downstream of canonical Wnt signaling to control cell proliferation in the developing tectum

Nyholm et al., 2007

ZDB-PUB-070122-30
PMID:17215296