PUBLICATION

hrT is required for cardiovascular development in zebrafish

Authors

Szeto, D.P., Griffin, K.J.P., and Kimelman, D.

ID

ZDB-PUB-021105-11

Date

2002

Source

Development (Cambridge, England) 129(21): 5903-5101 (Journal)

Registered Authors

Griffin, Kevin, Kimelman, David, Szeto, Daniel P.

Keywords

zebrafish; hrT; cardiogenesis; dorsal aorta; tbx5; fli1; floating head

MeSH Terms

Zebrafish/embryology*
Zebrafish/genetics*
Animals
T-Box Domain Proteins/genetics*
T-Box Domain Proteins/physiology
Hematopoiesis/genetics
Hematopoiesis/physiology
Cardiovascular System/embryology*
Recombinant Fusion Proteins/genetics
In Situ Hybridization
Homeodomain Proteins/genetics
Homeodomain Proteins/physiology
Heart Defects, Congenital/embryology
Heart Defects, Congenital/genetics
Mutation
Gene Expression Regulation, Developmental
Mice
Oligodeoxyribonucleotides, Antisense/genetics
Oligodeoxyribonucleotides, Antisense/pharmacology
Humans
Transcription Factors/genetics
Transcription Factors/physiology
Zebrafish Proteins*

(all 23)

PubMed

12397116 Full text @ Development

Abstract

The recently identified zebrafish T-box gene hrT is expressed in the developing heart and in the endothelial cells forming the dorsal aorta. Orthologs of hrT are expressed in cardiovascular cells from Drosophila to mouse, suggesting that the function of hrT is evolutionarily conserved. The role of hrT in cardiovascular development, however, has not thus far been determined in any animal model. Using morpholino antisense oligonucleotides, we show that zebrafish embryos lacking hrT function have dysmorphic hearts and an absence of blood circulation. Although the early events in heart formation were normal in hrT morphant embryos, subsequently the hearts failed to undergo looping, and late onset defects in chamber morphology and gene expression were observed. In particular, we found that the loss of hrT function led to a dramatic upregulation of tbx5, a gene required for normal heart morphogenesis. Conversely, we show that overexpression of hrT causes a significant downregulation of tbx5, indicating that one key role of hrT is to regulate the levels of tbx5. Secondly, we found that HrT is required to inhibit the expression of the blood lineage markers gata1 and gata2 in the most posterior lateral plate mesoderm. Finally, we show that HrT is required for vasculogenesis in the trunk, leading to similar vascular defects to those observed in midline mutants such as floating head. hrT expression in the vascular progenitors depends upon midline mesoderm, indicating that this expression is one important component of the response to a midline-derived signal during vascular morphogenesis.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
fli1	AB	standard conditions	Prim-5	dorsal aorta	ISH	Fig. 4
fli1	AB	standard conditions	Prim-5	intersegmental vessel	ISH	Fig. 4
fli1	AB	standard conditions	Prim-5	median axial vein	ISH	Fig. 4
fli1	AB	standard conditions	Prim-15	unspecified	ISH	Fig. 4
fli1	AB	standard conditions	10-13 somites to 20-25 somites	unspecified	ISH	Fig. 4
fli1	AB + MO1-tbx20	standard conditions	Prim-5	dorsal aorta	ISH	Fig. 4
fli1	AB + MO1-tbx20	standard conditions	Prim-5	intersegmental vessel	ISH	Fig. 4
fli1	AB + MO1-tbx20	standard conditions	Prim-5	median axial vein	ISH	Fig. 4
fli1	AB + MO1-tbx20	standard conditions	Prim-15	unspecified	ISH	Fig. 4
fli1	AB + MO1-tbx20	standard conditions	10-13 somites to 20-25 somites	unspecified	ISH	Fig. 4

1 - 10 of 41

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB + MO1-tbx20	standard conditions	Prim-25	blood circulation arrested, abnormal	text only
AB + MO1-tbx20	standard conditions	Prim-25	circulatory system development disrupted, abnormal	text only
AB + MO1-tbx20	standard conditions	Prim-25	heart tube morphology, abnormal	text only
AB + MO1-tbx20	standard conditions	Prim-25	pericardium edematous, abnormal	text only
AB + MO1-tbx20	standard conditions	1-4 somites to 10-13 somites	hemopoiesis disrupted, abnormal	Fig. 4
AB + MO1-tbx20	standard conditions	20-25 somites to Prim-5	blood vessel development disrupted, abnormal	Fig. 4
AB + MO1-tbx20	standard conditions	20-25 somites to Prim-5	vascular cord morphology, abnormal	Fig. 4
AB + MO1-tbx20	standard conditions	Prim-5	blood vessel development disrupted, abnormal	Fig. 4
AB + MO1-tbx20	standard conditions	Prim-5	intersegmental vessel aplastic, abnormal	Fig. 4
AB + MO1-tbx20	standard conditions	Prim-5	trunk vasculature morphology, abnormal	Fig. 4

1 - 10 of 20

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
tm229		Point Mutation	noto

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
tbx20	MO1-tbx20	MRPHLNO
tbx20	MO2-tbx20	MRPHLNO

Fish

Fish
AB
AB + MO1-tbx20
AB + MO2-tbx20
noto^tm229/tm229 (AB)

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Szeto et al., 2002 ZDB-PUB-021105-11 PMID:12397116

hrT is required for cardiovascular development in zebrafish

Szeto et al., 2002

ZDB-PUB-021105-11
PMID:12397116