PUBLICATION

Kctd15 inhibits neural crest formation by attenuating Wnt/β-catenin signaling output

Authors

Dutta, S., and Dawid, I.B.

ID

ZDB-PUB-100806-22

Date

2010

Source

Development (Cambridge, England) 137(18): 3013-3018 (Journal)

Registered Authors

Dawid, Igor B., Dutta, Sunit

Keywords

Neural crest, Neural plate border, Wnt signaling, Pigmentation, BTB domain, Zebrafish, Xenopus

MeSH Terms

Wnt Proteins/genetics
Wnt Proteins/metabolism
Signal Transduction*
Animals
Xenopus laevis/embryology
Xenopus laevis/genetics
Xenopus laevis/metabolism*
Zebrafish/embryology
Zebrafish/genetics
Zebrafish/metabolism*
Xenopus Proteins/genetics
Xenopus Proteins/metabolism*
Cell Differentiation
Gene Expression Regulation, Developmental
beta Catenin/genetics
beta Catenin/metabolism
Neural Crest/embryology*
Neural Crest/metabolism*
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Potassium Channels, Voltage-Gated/genetics
Potassium Channels, Voltage-Gated/metabolism*

(all 22)

PubMed

20685732 Full text @ Development

Abstract

Neural crest (NC) precursors are stem cells that are capable of forming many cell types after migration to different locations in the embryo. NC and placodes form at the neural plate border (NPB). The Wnt pathway is essential for specifying NC versus placodal identity in this cell population. Here we describe the BTB domain-containing protein Potassium channel tetramerization domain containing 15 (Kctd15) as a factor expressed in the NPB that efficiently inhibits NC induction in zebrafish and frog embryos. Whereas overexpression of Kctd15 inhibited NC formation, knockdown of Kctd15 led to expansion of the NC domain. Likewise, NC induction by Wnt3a plus Chordin in Xenopus animal explants was suppressed by Kctd15, but constitutively active beta-catenin reversed Kctd15-mediated suppression of NC induction. Suppression of NC induction by inhibition of Wnt8.1 was rescued by reduction of Kctd15 expression, linking Kctd15 action to the Wnt pathway. We propose that Kctd15 inhibits NC formation by attenuating the output of the canonical Wnt pathway, thereby restricting expansion of the NC domain beyond its normal range.

Genes / Markers

Figures

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Expression

Fish	Conditions	Stage	Anatomy	Assay	Figure
WT	control	Prim-5	pharyngeal arch	ISH	Fig. 2
WT	control	Prim-5	telencephalon	ISH	Fig. 2
WT + MO1-kctd15a + MO1-kctd15b	standard conditions	Prim-5	pharyngeal arch	ISH	Fig. 2
WT + MO1-kctd15a + MO1-kctd15b	standard conditions	Prim-5	telencephalon	ISH	Fig. 2
WT	standard conditions	1-4 somites	neural plate	ISH	Fig. 1
WT	standard conditions	1-4 somites	neural crest cell	ISH	Fig. 1
WT	control	1-4 somites	neural crest cell	ISH	Fig. 2
WT	control	1-4 somites	neural crest cell	ISH	Fig. 3
WT	control	1-4 somites	notochord	ISH	Fig. 3
WT	control	1-4 somites	notochord	ISH	Fig. 2

1 - 10 of 31

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-kctd15a + MO1-kctd15b	standard conditions	Prim-5	cell death increased occurrence, abnormal	Fig. 1
WT + MO1-kctd15a + MO1-kctd15b	standard conditions	Prim-5	head decreased size, abnormal	Fig. 1
WT + MO1-kctd15a + MO1-kctd15b	standard conditions	Prim-5	somite morphology, abnormal	Fig. 1
WT + MO1-kctd15a + MO1-kctd15b	standard conditions	Protruding-mouth	mandibular arch skeleton aplastic, abnormal	Fig. 1
WT + MO1-kctd15a + MO1-kctd15b	standard conditions	Protruding-mouth	pharyngeal arch morphology, abnormal	Fig. 1
WT + MO1-kctd15a + MO1-kctd15b	standard conditions	Protruding-mouth	pigmentation increased occurrence, abnormal	Fig. 1
WT + MO1-wnt8a	standard conditions	1-4 somites	neural crest cell differentiation disrupted, abnormal	Fig. 3
WT + MO1-wnt8a	standard conditions	1-4 somites	neural crest cell morphology, abnormal	Fig. 3

1 - 8 of 8

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
w25Tg	Tg(top:GFP)	Transgenic Insertion

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
kctd15a	MO1-kctd15a	MRPHLNO
kctd15b	MO1-kctd15b	MRPHLNO
wnt8a	MO1-wnt8a	MRPHLNO

Fish

Fish
WT
WT + MO1-kctd15a + MO1-kctd15b
WT + MO1-kctd15a + MO1-kctd15b + MO1-wnt8a
WT + MO1-wnt8a

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
GFP	EFG	GFP

Mapping

Dutta et al., 2010 ZDB-PUB-100806-22 PMID:20685732

Kctd15 inhibits neural crest formation by attenuating Wnt/β-catenin signaling output

Dutta et al., 2010

ZDB-PUB-100806-22
PMID:20685732