PUBLICATION

Regulation of canonical Wnt signaling by Brachyury is essential for posterior mesoderm formation

Authors

Martin, B.L., and Kimelman, D.

ID

ZDB-PUB-080714-9

Date

2008

Source

Developmental Cell 15(1): 121-133 (Journal)

Registered Authors

Kimelman, David, Martin, Benjamin

Keywords

none

MeSH Terms

Protein Structure, Tertiary
Gene Expression Regulation, Developmental
Zebrafish Proteins/chemistry
Zebrafish Proteins/genetics
Zebrafish Proteins/physiology*
Oligonucleotides, Antisense/pharmacology
Somites/embryology
Models, Biological
Fetal Proteins
Body Patterning/physiology
Animals
Immunohistochemistry
Signal Transduction*
MyoD Protein/metabolism
Embryo, Nonmammalian/physiology
T-Box Domain Proteins/chemistry
T-Box Domain Proteins/genetics
T-Box Domain Proteins/physiology*
Mutation
Mesoderm/physiology*
Wnt Proteins/physiology*
In Situ Hybridization
Microinjections
Zebrafish/embryology*
Zebrafish/genetics

(all 25)

PubMed

18606146 Full text @ Dev. Cell

Abstract

The T box transcription factor Brachyury is essential for the formation of the posterior body in all vertebrates, although its critical transcriptional targets have remained elusive. Loss-of-function studies of mouse Brachyury and the zebrafish Brachyury ortholog Ntl indicated that Brachyury plays a more significant role in higher vertebrates than lower vertebrates. We have identified a second zebrafish Brachyury ortholog (Bra), and show that a combined loss of Ntl and Bra recapitulates the mouse phenotype, demonstrating an ancient role for Brachyury in patterning all but the most anterior somites. Using cell transplantation, we show that the only essential role for Brachyury during somite formation is non-cell autonomous, and demonstrate that Ntl and Bra are required for and can induce expression of the canonical Wnts wnt8 and wnt3a. We propose that a positive autoregulatory loop between Ntl/Bra and canonical Wnt signaling maintains the mesodermal progenitors to facilitate posterior somite development in chordates.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
etv4	tbxta^b195/b195	standard conditions	1-4 somites	axial mesoderm	ISH	Fig. 5
etv4	tbxta^b195/b195	standard conditions	Bud	axial mesoderm	ISH	Fig. 5
etv4	tbxta^b195/b195	standard conditions	Shield	margin	ISH	Fig. 5
etv4	tbxta^b195/b195	standard conditions	75%-epiboly	margin	ISH	Fig. 5
etv4	tbxta^b195/b195 + MO2-tbxtb	standard conditions	1-4 somites	axial mesoderm	ISH	Fig. 5
etv4	tbxta^b195/b195 + MO2-tbxtb	standard conditions	Bud	axial mesoderm	ISH	Fig. 5
etv4	tbxta^b195/b195 + MO2-tbxtb	standard conditions	75%-epiboly	margin	ISH	Fig. 5
etv4	tbxta^b195/b195 + MO2-tbxtb	standard conditions	Shield	margin	ISH	Fig. 5
etv4	w26Tg	heat shock	5-9 somites	tail bud	ISH	Fig. S4
etv4	w26Tg	standard conditions	5-9 somites	tail bud	ISH	Fig. S4

1 - 10 of 103

Show

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
tbxta^b195/b195	standard conditions	Prim-5	post-vent region decreased length, abnormal	Fig. 2
tbxta^b195/b195	standard conditions	Prim-5	somite decreased amount, abnormal	Fig. 2
tbxta^b195/b195	standard conditions	Prim-5	somite decreased size, abnormal	Fig. 2
tbxta^b195/b195	standard conditions	Prim-5	somite morphology, abnormal	Fig. 2
tbxta^b195/b195 + MO1-tbxtb + MO4-tp53	standard conditions	Prim-5	post-vent region decreased length, abnormal	Fig. 2
tbxta^b195/b195 + MO1-tbxtb + MO4-tp53	standard conditions	Prim-5	somite decreased amount, abnormal	Fig. 2
tbxta^b195/b195 + MO1-tbxtb + MO4-tp53	standard conditions	Prim-5	somite decreased size, abnormal	Fig. 2
tbxta^b195/b195 + MO1-tbxtb + MO4-tp53	standard conditions	Prim-5	somite morphology, abnormal	Fig. 2
tbxta^b195/b195 + MO2-tbxtb	standard conditions	Prim-5	post-vent region decreased length, abnormal	Fig. 2
tbxta^b195/b195 + MO2-tbxtb	standard conditions	Prim-5	somite decreased amount, abnormal	Fig. 2

1 - 10 of 12

Show

Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
b195		Insertion	tbxta
w26Tg	Tg(hsp70l:tcf7l1a-GFP)	Transgenic Insertion
w32Tg	Tg(hsp70l:dkk1b-GFP)	Transgenic Insertion

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
tbxta	MO3-tbxta	MRPHLNO
tbxtb	MO1-tbxtb	MRPHLNO
tbxtb	MO2-tbxtb	MRPHLNO
tp53	MO4-tp53	MRPHLNO

Fish

Fish
tbxta^b195/b195
tbxta^b195/b195 + MO1-tbxtb + MO4-tp53
tbxta^b195/b195 + MO2-tbxtb
w26Tg
w32Tg
WIK/AB
WT
WT + MO2-tbxtb

Antibodies

Orthology

Gene	Orthology
tbxtb

Engineered Foreign Genes

Marker	Marker Type	Name
GFP	EFG	GFP

Mapping

Martin et al., 2008 ZDB-PUB-080714-9 PMID:18606146

Regulation of canonical Wnt signaling by Brachyury is essential for posterior mesoderm formation

Martin et al., 2008

ZDB-PUB-080714-9
PMID:18606146