PUBLICATION

Tbx1 controls the morphogenesis of pharyngeal pouch epithelia through mesodermal Wnt11r and Fgf8a

Authors

Choe, C.P., Crump, J.G.

ID

ZDB-PUB-140822-6

Date

2014

Source

Development (Cambridge, England) 141(18): 3583-93 (Journal)

Registered Authors

Crump, Gage DeKoeyer

Keywords

none

MeSH Terms

Models, Biological
Cell Movement/physiology
Wnt Proteins/metabolism*
Animals
Fibroblast Growth Factors/metabolism*
Mesoderm/metabolism*
Organogenesis/physiology*
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Epithelium/physiology*
Zebrafish
Time-Lapse Imaging
Pharynx/embryology*
T-Box Domain Proteins/genetics
T-Box Domain Proteins/metabolism*

(all 15)

PubMed

25142463 Full text @ Development

Abstract

The pharyngeal pouches are a segmental series of epithelial structures that organize the embryonic vertebrate face. In mice and zebrafish that carry mutations in homologs of the DiGeorge syndrome gene TBX1, a lack of pouches correlates with severe craniofacial defects, yet how Tbx1 controls pouch development remains unclear. Using mutant and transgenic rescue experiments in zebrafish, we show that Tbx1 functions in the mesoderm to promote the morphogenesis of pouch-forming endoderm through wnt11r and fgf8a expression. Consistently, compound losses of wnt11r and fgf8a phenocopy tbx1 mutant pouch defects, and mesoderm-specific restoration of Wnt11r and Fgf8a rescues tbx1 mutant pouches. Time-lapse imaging further reveals that Fgf8a acts as a Wnt11r-dependent guidance cue for migrating pouch cells. We therefore propose a two-step model in which Tbx1 coordinates the Wnt-dependent epithelial destabilization of pouch-forming cells with their collective migration towards Fgf8a-expressing mesodermal guideposts.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
d2EGFP	el72Tg; pt6Tg	standard conditions	Prim-15	pharyngeal endoderm	IFL	Fig. 1
d2EGFP	el72Tg; pt6Tg	standard conditions	Prim-5	pharyngeal endoderm	IFL	Fig. 5
d2EGFP	el72Tg; pt6Tg	standard conditions	Prim-15	pharyngeal endoderm	IFL	Fig. 5
d2EGFP	el72Tg; pt6Tg	standard conditions	Prim-15	pharyngeal mesoderm	IFL	Fig. 1
d2EGFP	fgf8a^{ti282a/ti282a}; el72Tg; pt6Tg	standard conditions	Prim-15	pharyngeal endoderm	IFL	Fig. 5
d2EGFP	fgf8a^{ti282a/ti282a}; el72Tg; pt6Tg	standard conditions	Prim-5	pharyngeal endoderm	IFL	Fig. 5
d2EGFP	tbx1^tu285/tu285; el72Tg; pt6Tg	standard conditions	Prim-15	pharyngeal endoderm	IFL	Fig. 1
d2EGFP	tbx1^tu285/tu285; el72Tg; pt6Tg	standard conditions	Prim-15	pharyngeal mesoderm	IFL	Fig. 1
dlx2a	ne1911Tg	standard conditions	Prim-15	pharyngeal arch	ISH	Fig. 2
dlx2a	tbx1^tu285/tu285; el493Tg; el513Tg; ne1911Tg	standard conditions	Prim-15	pharyngeal arch	ISH	Fig. 2

1 - 10 of 73

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
fgf8a^{ti282a/ti282a}	standard conditions	Prim-15	pharyngeal pouch decreased amount, abnormal	Fig. 4
fgf8a^{ti282a/ti282a}	standard conditions	Day 5	ceratobranchial cartilage decreased amount, abnormal	Fig. 4
fgf8a^{ti282a/ti282a}; el72Tg; pt6Tg	standard conditions	Prim-5 to Prim-15	pharyngeal pouch epithelial cell migration process quality, abnormal	Fig. 5
fgf8a^{ti282a/ti282a}; el72Tg; pt6Tg	standard conditions	Prim-5 to Prim-15	pharyngeal pouch pharyngeal system development process quality, abnormal	Fig. 5
fgf8a^{ti282a/ti282a}; wnt11^fh224/fh224	standard conditions	Prim-15	pharyngeal pouch decreased amount, abnormal	Fig. 4
fgf8a^{ti282a/ti282a}; wnt11^fh224/fh224	standard conditions	Day 5	ceratobranchial cartilage decreased amount, abnormal	Fig. 4
tbx1^tu285/tu285	standard conditions	Prim-15	ceratobranchial cartilage absent, abnormal	Fig. 2
tbx1^tu285/tu285	standard conditions	Prim-15	ceratobranchial cartilage absent, abnormal	Fig. 3
tbx1^tu285/tu285	standard conditions	Prim-15	pharyngeal arch cartilage malformed, abnormal	Fig. 2
tbx1^tu285/tu285	standard conditions	Prim-15	pharyngeal arch cartilage malformed, abnormal	Fig. 3

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
el8Tg	Tg(sox10:LOXP-GFP-LOXP-Hsa.DLX3)	Transgenic Insertion
el72Tg	Tg(her5:mCherry-CAAX)	Transgenic Insertion
el83Tg	Tg(nkx2.5:EGFP)	Transgenic Insertion
el493Tg	Tg(nkx2.5:tbx1,cryaa:Cerulean)	Transgenic Insertion
el513Tg	Tg(nkx2.3:tbx1,myl7:EGFP)	Transgenic Insertion
el562Tg	Tg(nkx2.5:fgf8a-GFP)	Transgenic Insertion
el567Tg	Tg(nkx2.5:wnt11,myl7:EGFP)	Transgenic Insertion
fh224		Point Mutation	wnt11
ne1911Tg	Tg(-3.4her5:EGFP)	Transgenic Insertion
pt6Tg	Tg(dusp6:d2EGFP)	Transgenic Insertion

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Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
el8Tg
el72Tg
el72Tg; el83Tg
el72Tg; pt6Tg
el83Tg
el493Tg
el513Tg
el562Tg
el562Tg; el72Tg
el567Tg

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
Cerulean	EFG	Cerulean
d2EGFP	EFG	d2EGFP
EGFP	EFG	EGFP
GFP	EFG	GFP
mCherry	EFG	mCherry

Mapping

Choe et al., 2014 ZDB-PUB-140822-6 PMID:25142463

Tbx1 controls the morphogenesis of pharyngeal pouch epithelia through mesodermal Wnt11r and Fgf8a

Choe et al., 2014

ZDB-PUB-140822-6
PMID:25142463